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## Question

# Gene Research for Functional Annotation

## ⚠️ CRITICAL: Gene/Protein Identification Context

**BEFORE YOU BEGIN RESEARCH:** You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

### Target Gene/Protein Identity (from UniProt):
- **UniProt Accession:** Q8N8Y2
- **Protein Description:** RecName: Full=V-type proton ATPase subunit d 2; Short=V-ATPase subunit d 2; AltName: Full=Vacuolar proton pump subunit d 2;
- **Gene Information:** Name=ATP6V0D2;
- **Organism (full):** Homo sapiens (Human).
- **Protein Family:** Belongs to the V-ATPase V0D/AC39 subunit family.
- **Key Domains:** ATPase_csu/dsu_sf. (IPR036079); ATPase_V0-cplx_csu/dsu. (IPR002843); ATPase_V0-cplx_dsu. (IPR016727); V-type_ATPase_csu/dsu. (IPR035067); V-type_ATPase_csu/dsu_dom_3. (IPR044911)

### MANDATORY VERIFICATION STEPS:

1. **Check if the gene symbol "ATP6V0D2" matches the protein description above**
2. **Verify the organism is correct:** Homo sapiens (Human).
3. **Check if protein family/domains align with what you find in literature**
4. **If you find literature for a DIFFERENT gene with the same or similar symbol, STOP**

### If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

**DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE.** Instead:
- State clearly: "The gene symbol 'ATP6V0D2' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

### Research Target:

Please provide a comprehensive research report on the gene **ATP6V0D2** (gene ID: ATP6V0D2, UniProt: Q8N8Y2) in human.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

## Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

# Gene Research for Functional Annotation

## ⚠️ CRITICAL: Gene/Protein Identification Context

**BEFORE YOU BEGIN RESEARCH:** You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

### Target Gene/Protein Identity (from UniProt):
- **UniProt Accession:** Q8N8Y2
- **Protein Description:** RecName: Full=V-type proton ATPase subunit d 2; Short=V-ATPase subunit d 2; AltName: Full=Vacuolar proton pump subunit d 2;
- **Gene Information:** Name=ATP6V0D2;
- **Organism (full):** Homo sapiens (Human).
- **Protein Family:** Belongs to the V-ATPase V0D/AC39 subunit family.
- **Key Domains:** ATPase_csu/dsu_sf. (IPR036079); ATPase_V0-cplx_csu/dsu. (IPR002843); ATPase_V0-cplx_dsu. (IPR016727); V-type_ATPase_csu/dsu. (IPR035067); V-type_ATPase_csu/dsu_dom_3. (IPR044911)

### MANDATORY VERIFICATION STEPS:

1. **Check if the gene symbol "ATP6V0D2" matches the protein description above**
2. **Verify the organism is correct:** Homo sapiens (Human).
3. **Check if protein family/domains align with what you find in literature**
4. **If you find literature for a DIFFERENT gene with the same or similar symbol, STOP**

### If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

**DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE.** Instead:
- State clearly: "The gene symbol 'ATP6V0D2' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

### Research Target:

Please provide a comprehensive research report on the gene **ATP6V0D2** (gene ID: ATP6V0D2, UniProt: Q8N8Y2) in human.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive Research Report: Human ATP6V0D2 (UniProt Q8N8Y2)

Plan status
- Identity verification: ATP6V0D2 encodes the V‑ATPase V0 sector d-subunit isoform 2 in human; literature below is restricted to human V‑ATPase and human cell systems where noted (completed). (chen2024vatpaseincancer pages 1-3)
- Evidence collection: Recent primary and review literature prioritizing 2023–2025 identified and synthesized (completed). (chen2024vatpaseincancer pages 1-3, chen2025theemergingroles pages 2-5, li2025atractylenolideiinhibits pages 11-14, li2025atractylenolideiinhibits pages 7-9, li2025atractylenolideiinhibits pages 16-17)

1) Key concepts and definitions (current understanding)
- Molecular identity and complex membership: ATP6V0D2 is a subunit of the membrane-embedded V0 sector of the vacuolar-type H+‑ATPase (V‑ATPase). The V‑ATPase consists of a cytosolic catalytic V1 sector (A–H subunits) and a membrane V0 sector (a, c/cʺ, d, e); the V1 central shaft (D/F) couples to V0 through the small d subunit. ATP6V0D2 encodes the d2 isoform of this V0 d subunit and participates in proton pumping through its structural role in the assembled holoenzyme. Isoform specialization is a hallmark of the V‑ATPase, with cell-type and organelle-specific distributions across subunits. (Cell Communication and Signaling, Dec 2024; URL: https://doi.org/10.1186/s12964-024-01998-9). (chen2024vatpaseincancer pages 1-3)
- Subcellular localization: In human cells, ATP6V0D2 localizes to lysosomes/acidic vesicles, where it contributes to lysosomal acidification and degradative capacity (Autophagy, Nov 2025; URL: https://doi.org/10.1080/15548627.2024.2421699). (li2025atractylenolideiinhibits pages 11-14, li2025atractylenolideiinhibits pages 7-9)
- Functional role (general): As part of V‑ATPase, ATP6V0D2 supports organelle acidification that underpins autophagic flux, cargo degradation, and, when situated at specialized membranes, extracellular acidification-dependent processes. Reviews emphasize subunit/isoform diversity and regulation (e.g., reversible V1–V0 assembly, subcellular trafficking) as core determinants of activity. (Biomolecules, Apr 2025; URL: https://doi.org/10.3390/biom15040525). (chen2025theemergingroles pages 2-5)

2) Recent developments and latest research (prioritize 2023–2024+)
- Autophagosome–lysosome fusion mechanism linked to ATP6V0D2 (human tumor cells): A 2025 study in clear‑cell renal cell carcinoma (ccRCC) reports that ATP6V0D2 directly promotes autophagosome–lysosome fusion by physically interacting with RAB7 and HOPS complex components (e.g., VPS41), thereby facilitating HOPS assembly and SNARE complex formation. Co‑IP, GST pulldown with recombinant proteins (GST‑ATP6V0D2, His‑RAB7, His‑VPS41), and confocal colocalization in 786O and 293T cells support direct or complex-mediated binding. Knockdown of ATP6V0D2 reduced RAB7–VPS41 colocalization and impaired fusion, while pharmacologic upregulation of ATP6V0D2 restored fusion and autophagic flux (Autophagy, Nov 2025; URL: https://doi.org/10.1080/15548627.2024.2421699). (li2025atractylenolideiinhibits pages 11-14, li2025atractylenolideiinhibits pages 16-17)
- Lysosomal acidification and degradation in human cells: The same study shows ATP6V0D2 enhances lysosomal acidification and activity: depletion increased RFP+GFP+ LC3 puncta (indicating impaired fusion/degradation) and stabilized a lysosome‑degraded substrate (EPAS1/HIF2α). Chloroquine (lysosomal inhibitor) phenocopied the effect and eliminated differences between control and ATP6V0D2‑depleted cells, consistent with a role in the degradative step. Quantitatively, in vitro assays used ATL‑I at 80 μM for 48 h and xenografts used ATL‑I 50 mg/kg (with or without 20 mg/kg sunitinib) to modulate ATP6V0D2‑dependent autophagy and tumor phenotypes. Overexpression of ATP6V0D2 modestly increased apoptosis (~10% in 786O) while reducing tumor burden in xenografts. Publication date: Nov 2025. (li2025atractylenolideiinhibits pages 7-9)
- Immune/macrophage context (recent reviews citing primary work): Reviews summarizing macrophage studies indicate that ATP6V0D2 facilitates autophagosome–lysosome fusion to restrain inflammasome activation and bacterial infection, situating ATP6V0D2 as an immune-regulatory V‑ATPase subunit with cell-type preferential expression (Biomolecules, Apr 2025; URL: https://doi.org/10.3390/biom15040525). (chen2025theemergingroles pages 26-26)
- Structural/architectural updates on V‑ATPase relevant to ATP6V0D2: A 2024 review details human V‑ATPase subunit composition, regulation (assembly/disassembly), and roles in pH homeostasis and disease microenvironments, reinforcing the placement of ATP6V0D2 within V0 and its potential to shape organelle acidity and flux (Cell Communication and Signaling, Dec 2024; URL: https://doi.org/10.1186/s12964-024-01998-9). (chen2024vatpaseincancer pages 1-3)

3) Current applications and real-world implementations
- Oncology: Targeting the autophagy–lysosome system via ATP6V0D2 shows translational potential in ccRCC. Pharmacologic upregulation of ATP6V0D2 with atractylenolide I (ATL‑I) promoted autophagic degradation of EPAS1/HIF2α, reduced VEGF signaling outputs, and overcame sunitinib resistance in xenografts, suggesting a route to modulate lysosomal flux and angiogenesis in therapy-resistant settings. Dosing in mice (ATL‑I 50 mg/kg; sunitinib 20 mg/kg) and cell-based ATL‑I exposure (80 μM, 48 h) are reported, providing actionable parameters for preclinical replication (Autophagy, Nov 2025; URL: https://doi.org/10.1080/15548627.2024.2421699). (li2025atractylenolideiinhibits pages 7-9)
- Immunology/infection: Reviews highlight that in macrophages ATP6V0D2 aids autophagosome–lysosome fusion to limit inflammasome activation and bacterial burdens, indicating potential for host-directed therapies enhancing lysosomal fusion/acidification in infection and inflammatory states (Biomolecules, Apr 2025; URL: https://doi.org/10.3390/biom15040525). (chen2025theemergingroles pages 26-26)
- Broad V‑ATPase targeting: State-of-the-art reviews discuss V‑ATPase as a therapeutic axis (e.g., cancer metabolism, tumor microenvironment acidity, autophagy dependence), providing the rationale for modulating specific subunits/isoforms, including d2, in a context-dependent manner (Cell Communication and Signaling, Dec 2024; URL: https://doi.org/10.1186/s12964-024-01998-9). (chen2024vatpaseincancer pages 1-3)

4) Expert opinions and analysis (authoritative sources)
- V‑ATPase architecture and isoform specialization underscore ATP6V0D2’s context-specific biology: Expert reviews emphasize that subunit isoforms (including d2) confer organelle and tissue specificity to V‑ATPase function, affecting localization, activity, and signaling crosstalk (e.g., mTORC1/AMPK at lysosomes). This supports interpreting ATP6V0D2 phenotypes as isoform-dependent tuning of acidification and degradative flux in select cell types. Publication: Dec 2024; URL: https://doi.org/10.1186/s12964-024-01998-9. (chen2024vatpaseincancer pages 1-3)
- Lysosomal energy-sensing platforms: Reviews place V‑ATPase at the core of lysosomal signaling hubs that integrate nutrient status with autophagy and inflammatory outputs, strengthening the view that ATP6V0D2 may influence not only proton pumping mechanics but also upstream assembly and downstream fusion/flux control in disease states (Biomolecules, Jul 2025; URL: https://doi.org/10.3390/biom15070997; Biomolecules, Apr 2025; URL: https://doi.org/10.3390/biom15040525). (yang2025vatpaseandlysosomal pages 6-7, chen2025theemergingroles pages 2-5)

5) Relevant statistics and data from recent studies
- Human ccRCC systems: ATL‑I upregulated ATP6V0D2 and restored autophagosome–lysosome fusion; ATP6V0D2 knockdown increased RFP+GFP+ LC3 puncta, stabilized EPAS1/HIF2α (relative to control), and reduced RAB7–VPS41 colocalization; ATL‑I at 80 μM (48 h) used for in vitro; xenograft dosing at 50 mg/kg for ATL‑I with or without 20 mg/kg sunitinib; ATP6V0D2 overexpression increased apoptosis by ~10% in 786O cells (Autophagy, Nov 2025; URL: https://doi.org/10.1080/15548627.2024.2421699). (li2025atractylenolideiinhibits pages 11-14, li2025atractylenolideiinhibits pages 7-9, li2025atractylenolideiinhibits pages 16-17)
- System-level context: Reviews synthesize that V‑ATPase-dependent lysosomal pH typically falls in the 4.5–5.0 range in human cells and that isoform composition, assembly state, and subcellular targeting regulate acidification and flux, providing quantitative context for interpreting ATP6V0D2 perturbations (Biomolecules, Apr 2025; URL: https://doi.org/10.3390/biom15040525). (chen2025theemergingroles pages 2-5)

Mechanistic model (integrated)
- ATP6V0D2 functions as a V0 d‑subunit isoform in the V‑ATPase, promoting lysosomal acidification and autophagic cargo degradation. Beyond proton pumping, it facilitates autophagosome–lysosome fusion by engaging RAB7–HOPS machinery and enabling SNARE assembly at the fusion stage. In human tumor cells, this supports degradation of disease-relevant substrates (EPAS1/HIF2α), modulates angiogenic signaling, and can influence therapy resistance. In immune cells (macrophages), ATP6V0D2’s role in fusion/acidification contributes to dampening inflammasome activation and restricting intracellular pathogens. Collectively, ATP6V0D2 is best understood as an isoform-specific enabler of lysosomal function and fusion, with disease-relevant consequences in cancer and infection. (chen2024vatpaseincancer pages 1-3, chen2025theemergingroles pages 26-26, li2025atractylenolideiinhibits pages 11-14, li2025atractylenolideiinhibits pages 7-9)

Identity cross-check and ambiguity safeguards
- Gene symbol and protein match: Literature consistently places ATP6V0D2 as the human V‑ATPase V0 d‑subunit isoform 2 within the V‑ATPase complex, distinct from catalytic V1 subunits and other V0 components; no conflicting gene/protein symbol usage was detected in 2024–2025 reviews and the cited human cell studies. (chen2024vatpaseincancer pages 1-3)
- Organism: Human-focused reviews and the ccRCC experimental systems (786O, 293T) confirm human context for functional claims. (li2025atractylenolideiinhibits pages 11-14, li2025atractylenolideiinhibits pages 7-9)
- Protein family: Placement within the V0 d-subunit family is consistent across structural/functional reviews, aligning with expected V‑ATPase domain architecture. (chen2024vatpaseincancer pages 1-3, chen2025theemergingroles pages 2-5)

Key evidence table
| Concept/Claim | Mechanistic detail | Experimental system (species/cell type) | Year | Key methods | Outcome / quantitative notes | Source URL | Citation ID |
|---|---|---|---:|---|---|---|---|
| Identity / complex membership | ATP6V0D2 encodes the V-ATPase V0 sector d‑subunit isoform 2 ("d2"); a membrane V0 component that links the V1 rotor to the proton-translocating pore; isoform-specific expression vs d1 (ubiquitous) | Human / mammalian (reviewed annotation and structural descriptions) | 2024–2025 | Protein family/domain annotation; structural reviews | Classified as V0 d‑subunit with tissue‑preferential isoform expression (d2 vs d1) | https://doi.org/10.1186/s12964-024-01998-9; https://doi.org/10.3390/biom15070997 | (chen2024vatpaseincancer pages 1-3, yang2025vatpaseandlysosomal pages 6-7) |
| Subcellular localization | Localizes to lysosomes / acidic vesicles (colocalizes with LAMP1); reported lysosomal membrane association and contribution to organellar acidification | Human cell lines (ccRCC 786O, 293T) and reviewed mammalian datasets | 2025 | IHC / IF, LysoTracker, colocalization, WB | Shows lysosomal localization and functional role in organelle acidification/activity | https://doi.org/10.1080/15548627.2024.2421699 | (li2025atractylenolideiinhibits pages 11-14, li2025atractylenolideiinhibits pages 7-9) |
| Autophagosome–lysosome fusion (RAB7–HOPS–SNARE axis) | Physically interacts with RAB7 and HOPS components (e.g., VPS41); promotes RAB7–HOPS interaction and facilitates SNARE complex assembly to drive autophagosome–lysosome fusion | Human 786O / SU‑R‑786O tumor cells, 293T transfections; recombinant protein pulldowns | 2025 | co‑IP, GST pulldown, mass spectrometry, confocal colocalization, RFP‑GFP‑LC3 flux, TEM | ATP6V0D2 knockdown reduces RAB7–VPS41 colocalization and impairs fusion; ATL‑I upregulates ATP6V0D2 and restores fusion | https://doi.org/10.1080/15548627.2024.2421699 | (li2025atractylenolideiinhibits pages 11-14, li2025atractylenolideiinhibits pages 16-17) |
| Lysosomal acidification & degradative activity | Promotes lysosomal acidification and degradative flux; loss impairs autophagic degradation (increased LC3/SQSTM1, more RFP+GFP+ LC3 puncta), stabilizes lysosome‑targeted substrates (e.g., EPAS1/HIF2α) | Human ccRCC cell lines; pharmacologic perturbations (chloroquine, rapamycin) | 2025 | LysoTracker, RFP‑GFP‑LC3 assay, western blot, cycloheximide chase, chloroquine inhibition, TEM | ATP6V0D2 depletion impairs autophagic flux and increases target stability; chloroquine phenocopies impaired degradation | https://doi.org/10.1080/15548627.2024.2421699 | (li2025atractylenolideiinhibits pages 7-9) |
| Osteoclast fusion / bone resorption roles | Expressed in osteoclast lineage; implicated in pre‑osteoclast fusion and the V‑ATPase‑dependent acidification steps required for bone resorption (works alongside fusion regulators such as DC‑STAMP) | Mouse and human osteoclast studies summarized in reviews and primary literature | 2023–2024 | Osteoclast differentiation assays, gene expression profiling, in vivo bone phenotyping (reviewed evidence) | Reviewed evidence links ATP6V0D2 to osteoclast fusion and resorptive function; loss/reduction reported to impair fusion and modulate bone remodeling (see primary studies cited in reviews) | https://doi.org/10.1186/s12964-024-01998-9; https://doi.org/10.3390/cells12212576 | (chen2024vatpaseincancer pages 1-3, chen2025theemergingroles pages 2-5) |
| Immune / macrophage roles & disease relevance | Macrophage‑specific functions include facilitating autophagosome–lysosome fusion to restrict inflammasome activation and bacterial infection; disease links reported in cancer (modulates degradation of oncogenic factors and therapy resistance), infection models, and links to atherosclerosis via autophagy–lysosome pathways | Macrophage studies, infection models, ccRCC cell lines, mouse models and transcriptomic analyses | 2024–2025 | Gene knockdown/overexpression, infection assays, xenografts, transcriptomics / bioinformatics | ATP6V0D2 modulates immune responses and infection outcomes; upregulation can enhance lysosomal degradation of disease‑relevant substrates and affect tumor progression / drug response | https://doi.org/10.3390/biom15040525; https://doi.org/10.1080/15548627.2024.2421699 | (chen2025theemergingroles pages 26-26, li2025atractylenolideiinhibits pages 11-14, chen2024vatpaseincancer pages 1-3) |


*Table: Compact summary table mapping key claims about human ATP6V0D2 to mechanistic details, experimental systems, methods, outcomes and source literature (2024–2025). Useful for quickly tracing major functional assertions to the supporting references.*

References (with URLs and dates)
- Chen T, Lin X, Lu S, Li B. V‑ATPase in cancer: mechanistic insights and therapeutic potentials. Cell Communication and Signaling. Dec 2024. URL: https://doi.org/10.1186/s12964-024-01998-9 (chen2024vatpaseincancer pages 1-3)
- Chen Y‑Y, Liu C‑X, Liu H‑X, Wen S‑Y. The emerging roles of V‑ATPase‑dependent lysosomal acidification in cardiovascular disease. Biomolecules. Apr 2025. URL: https://doi.org/10.3390/biom15040525 (chen2025theemergingroles pages 2-5)
- Yang X, Holliday LS. V‑ATPase and lysosomal energy sensing in periodontitis and MRONJ. Biomolecules. Jul 2025. URL: https://doi.org/10.3390/biom15070997 (yang2025vatpaseandlysosomal pages 6-7, yang2025vatpaseandlysosomal pages 4-6)
- Li Q et al. Atractylenolide I inhibits angiogenesis and reverses sunitinib resistance in clear cell renal cell carcinoma through ATP6V0D2‑mediated autophagic degradation of EPAS1/HIF2α. Autophagy. Nov 2025. URL: https://doi.org/10.1080/15548627.2024.2421699 (li2025atractylenolideiinhibits pages 11-14, li2025atractylenolideiinhibits pages 7-9, li2025atractylenolideiinhibits pages 16-17)
- Biomolecules review citing macrophage-specific ATP6V0D2 restraining inflammasome activation and bacterial infection via autophagosome–lysosome fusion. Apr 2025. URL: https://doi.org/10.3390/biom15040525 (chen2025theemergingroles pages 26-26)

Notes on evidence scope
- Osteoclast-specific primary mechanistic data were not directly captured in the 2023–2024 items retrieved here; however, expert reviews consistently assign ATP6V0D2 to osteoclast/acidification pathways through its role as a V0 d‑subunit and isoform specialization. Where osteoclast fusion/resorption roles are mentioned, they are supported here via reviews rather than newly retrieved 2023–2024 primary articles. Future updates should incorporate osteoclast-focused primary studies as they become available in 2023–2024 if accessible. (chen2024vatpaseincancer pages 1-3, chen2025theemergingroles pages 2-5)

References

1. (chen2024vatpaseincancer pages 1-3): Tingting Chen, Xiaotan Lin, Shuo Lu, and Bo Li. V-atpase in cancer: mechanistic insights and therapeutic potentials. Cell Communication and Signaling : CCS, Dec 2024. URL: https://doi.org/10.1186/s12964-024-01998-9, doi:10.1186/s12964-024-01998-9. This article has 15 citations.

2. (chen2025theemergingroles pages 2-5): Yan-Yan Chen, Cai-Xia Liu, Hai-Xin Liu, and Shi-Yuan Wen. The emerging roles of vacuolar-type atpase-dependent lysosomal acidification in cardiovascular disease. Biomolecules, 15:525, Apr 2025. URL: https://doi.org/10.3390/biom15040525, doi:10.3390/biom15040525. This article has 9 citations and is from a poor quality or predatory journal.

3. (li2025atractylenolideiinhibits pages 11-14): Qinyu Li, Kai Zeng, Qian Chen, Chenglin Han, Xi Wang, Beining Li, Jianping Miao, Bolong Zheng, Jihong Liu, Xianglin Yuan, and Bo Liu. Atractylenolide i inhibits angiogenesis and reverses sunitinib resistance in clear cell renal cell carcinoma through atp6v0d2-mediated autophagic degradation of epas1/hif2α. Autophagy, 21:619-638, Nov 2025. URL: https://doi.org/10.1080/15548627.2024.2421699, doi:10.1080/15548627.2024.2421699. This article has 20 citations and is from a domain leading peer-reviewed journal.

4. (li2025atractylenolideiinhibits pages 7-9): Qinyu Li, Kai Zeng, Qian Chen, Chenglin Han, Xi Wang, Beining Li, Jianping Miao, Bolong Zheng, Jihong Liu, Xianglin Yuan, and Bo Liu. Atractylenolide i inhibits angiogenesis and reverses sunitinib resistance in clear cell renal cell carcinoma through atp6v0d2-mediated autophagic degradation of epas1/hif2α. Autophagy, 21:619-638, Nov 2025. URL: https://doi.org/10.1080/15548627.2024.2421699, doi:10.1080/15548627.2024.2421699. This article has 20 citations and is from a domain leading peer-reviewed journal.

5. (li2025atractylenolideiinhibits pages 16-17): Qinyu Li, Kai Zeng, Qian Chen, Chenglin Han, Xi Wang, Beining Li, Jianping Miao, Bolong Zheng, Jihong Liu, Xianglin Yuan, and Bo Liu. Atractylenolide i inhibits angiogenesis and reverses sunitinib resistance in clear cell renal cell carcinoma through atp6v0d2-mediated autophagic degradation of epas1/hif2α. Autophagy, 21:619-638, Nov 2025. URL: https://doi.org/10.1080/15548627.2024.2421699, doi:10.1080/15548627.2024.2421699. This article has 20 citations and is from a domain leading peer-reviewed journal.

6. (chen2025theemergingroles pages 26-26): Yan-Yan Chen, Cai-Xia Liu, Hai-Xin Liu, and Shi-Yuan Wen. The emerging roles of vacuolar-type atpase-dependent lysosomal acidification in cardiovascular disease. Biomolecules, 15:525, Apr 2025. URL: https://doi.org/10.3390/biom15040525, doi:10.3390/biom15040525. This article has 9 citations and is from a poor quality or predatory journal.

7. (yang2025vatpaseandlysosomal pages 6-7): Xianrui Yang and Lexie Shannon Holliday. V-atpase and lysosomal energy sensing in periodontitis and medicine-related osteonecrosis of the jaw. Biomolecules, 15:997, Jul 2025. URL: https://doi.org/10.3390/biom15070997, doi:10.3390/biom15070997. This article has 1 citations and is from a poor quality or predatory journal.

8. (yang2025vatpaseandlysosomal pages 4-6): Xianrui Yang and Lexie Shannon Holliday. V-atpase and lysosomal energy sensing in periodontitis and medicine-related osteonecrosis of the jaw. Biomolecules, 15:997, Jul 2025. URL: https://doi.org/10.3390/biom15070997, doi:10.3390/biom15070997. This article has 1 citations and is from a poor quality or predatory journal.

## Citations

1. chen2024vatpaseincancer pages 1-3
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