Mitochondrial respiratory Complex II (succinate dehydrogenase) + assembly factors; SDHA/SDHB/SDHC/SDHD + SDHAF1/SDHAF2

Respiratory Complex II (succinate dehydrogenase, SDH) is the only enzyme shared between the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain. It oxidises succinate to fumarate in the matrix and feeds the released electrons into the ubiquinone pool, without pumping protons. The holoenzyme is a heterotetramer anchored in the inner membrane: the flavoprotein subunit SDHA carries a covalently bound FAD and the succinate-oxidising active site; the iron-sulfur subunit SDHB relays the electrons through three Fe-S clusters ([2Fe-2S], [4Fe-4S], [3Fe-4S]); and the two integral-membrane subunits SDHC and SDHD form the membrane anchor, bind a single heme b and provide the ubiquinone-reduction site. Two dedicated matrix assembly factors build the soluble catalytic head before it docks onto the membrane anchor: SDHAF2 (SDH5) promotes the covalent attachment of FAD to SDHA (flavinylation), and SDHAF1 — a LYR-motif protein acting with the HSC20/HSPA9 Fe-S co-chaperone system — delivers and inserts the iron-sulfur clusters into SDHB. Germline defects in the SDH subunits and assembly factors cause hereditary paraganglioma-pheochromocytoma syndromes and, when biallelic, mitochondrial complex II deficiency (Leigh syndrome, leukoencephalopathy, cardiomyopathy).

MODULE:mitochondrial_complex_iiDRAFTProtein Complexmodules/mitochondrial_complex_ii.yaml
mitochondrial electron transport, succinate to ubiquinoneGO:0006121 mitochondrial respiratory chain complex II assemblyGO:0034553
GO:0006121
mitochondrial electron transport, succinate to ubiquinone
The module is grounded in mitochondrial electron transport, succinate to ubiquinone (GO:0006121) — the reaction catalysed by Complex II.
GO:0034553
mitochondrial respiratory chain complex II assembly
The dedicated factors mediate mitochondrial respiratory chain complex II assembly (GO:0034553).
Reactome:R-HSA-70994
SDH complex dehydrogenates succinate
The catalytic reaction follows the human Reactome "SDH complex dehydrogenates succinate" reaction (R-HSA-70994).
file:human/SDHA/SDHA-ai-review.yaml
SDHA gene review (human)
The FAD flavoprotein / succinate-oxidising subunit (UniProtKB:P31040, GO:0000104) matches the completed human SDHA review (on main).
file:human/SDHB/SDHB-ai-review.yaml
SDHB gene review (human)
The iron-sulfur electron-transfer subunit (UniProtKB:P21912, GO:0009055) matches the completed human SDHB review (on main).
file:human/SDHC/SDHC-ai-review.yaml
SDHC gene review (human)
The heme-binding membrane-anchor subunit (UniProtKB:Q99643, GO:0020037) matches the completed human SDHC review (on main).
file:human/SDHD/SDHD-ai-review.yaml
SDHD gene review (human)
The heme-binding membrane-anchor subunit (UniProtKB:O14521, GO:0020037) matches the completed human SDHD review (on main).
file:human/SDHAF2/SDHAF2-ai-review.yaml
SDHAF2 gene review (human)
The SDHA flavinylation factor (UniProtKB:Q9NX18, GO:0044183/GO:0018293) matches the completed human SDHAF2 review.
file:human/SDHAF1/SDHAF1-ai-review.yaml
SDHAF1 gene review (human)
The SDHB Fe-S insertion factor (UniProtKB:A6NFY7, GO:0051087) matches the completed human SDHAF1 review.
3Nodes
2Parts
0Variant Sets
0Variants
6Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:mitochondrial_complex_ii deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

6 gene-function check(s) reflected in core functions · 0 conflict(s) · 4 evidence or coverage gap(s) (12 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
sdha_activity SDHA (human)
UniProtKB:P31040
Family Representative 		succinate dehydrogenase activity
GO:0000104 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sdhb_activity SDHB (human)
UniProtKB:P21912
Family Representative 		electron transfer activity
GO:0009055 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sdhc_activity SDHC (human)
UniProtKB:Q99643
Family Representative 		heme binding
GO:0020037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sdhd_activity SDHD (human)
UniProtKB:O14521
Family Representative 		heme binding
GO:0020037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sdhaf2_activity SDHAF2 (human)
UniProtKB:Q9NX18
Family Representative 		protein folding chaperone
GO:0044183 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sdhaf1_activity SDHAF1 (human)
UniProtKB:A6NFY7
Family Representative 		protein-folding chaperone binding
GO:0051087 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sdha_activity SDHA / flavoprotein subunit family
PANTHER:PTHR11632
Family 		succinate dehydrogenase activity
GO:0000104 		Family Scope Restricted
GO:0000104 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Complex II flavoproteins (SF51, SF53, SF72), as tca_cycle and mitochondrial_complex_ii assert on the base family, which also takes in the fumarate reductases. Desulfovibrio AprA in SF51 is a member exception.
sdhb_activity SDHB / iron-sulfur subunit family
PANTHER:PTHR11921
Family 		electron transfer activity
GO:0009055 		Family Supported
Family review supports GO:0009055 FAMILY_WIDE. Asserted by tca_cycle and mitochondrial_complex_ii; accepted by SDH2, SDHB and P. putida SdhB.
sdhc_activity SDHC / cytochrome b large membrane-anchor family
PANTHER:PTHR10978
Family 		heme binding
GO:0020037 		Family Supported
Family review supports GO:0020037 FAMILY_WIDE. Heme b binding, asserted by mitochondrial_complex_ii; SDHC accepts it.
sdhd_activity SDHD / cytochrome b small membrane-anchor family
Family 		heme binding
GO:0020037 		Family Id Missing
The family has no identifier linking it to a curated family review.
sdhaf2_activity SDHAF2 / SDH5 (Sdh5) flavinylation-factor family
PANTHER:PTHR12469
Family 		protein folding chaperone
GO:0044183 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0044183.
sdhaf1_activity SDHAF1 / LYR-motif Fe-S insertion-factor family
PANTHER:PTHR47046
Family 		protein-folding chaperone binding
GO:0051087 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR47046.

Gene-review completeness (6/6 grounded genes reviewed)

6 complete review(s) · 4 with deep research · 0 missing review · 2 reviewed but lacking deep research

Gene Review Complete Deep research
SDHA P31040 ✓ ✓ ✓
SDHAF1 A6NFY7 ✓ ✓ ✗
SDHAF2 Q9NX18 ✓ ✓ ✗
SDHB P21912 ✓ ✓ ✓
SDHC Q99643 ✓ ✓ ✓
SDHD O14521 ✓ ✓ ✓

Details

Context
mitochondrial inner membraneGO:0005743 mitochondrial matrixGO:0005759
Mitochondrial respiratory Complex II (succinate dehydrogenase)Protein Complexmitochondrial_complex_ii
mitochondrial electron transport, succinate to ubiquinoneGO:0006121 mitochondrial respiratory chain complex II assemblyGO:0034553
Context
mitochondrial inner membraneGO:0005743 mitochondrial matrixGO:0005759

Mitochondrial respiratory Complex II (succinate dehydrogenase), grounded to the human subunit and assembly-factor reviews: SDHA (P31040, GO:0000104 succinate dehydrogenase activity + contributes_to GO:0008177), SDHB (P21912, GO:0009055 electron transfer + contributes_to GO:0008177), SDHC (Q99643, GO:0020037 heme binding) and SDHD (O14521, GO:0020037 heme binding) are already reviewed on main and cited via file:; SDHAF2 (Q9NX18, GO:0044183 + protein-FAD linkage GO:0018293) and SDHAF1 (A6NFY7, GO:0051087) are curated here. The holoenzyme is modelled as a PROTEIN_COMPLEX node (only cofactor/ catalytic subunits carry the redox/heme MFs; the complex-level succinate dehydrogenase (quinone) activity GO:0008177 is a contributes_to relation on each subunit) plus an assembly-factor node that POSITIVELY_REGULATES it. Concepts GO:0006121 (succinate→ubiquinone electron transport) + GO:0034553 (Complex II assembly); catalytic reaction Reactome R-HSA-70994. The current Complex II membership term is GO:0045273 (GO:0045257 obsolete). Complex II feeds electrons into the ubiquinone pool shared with Complex I, then to Complex III → cytochrome c → Complex IV. Disorders: hereditary paraganglioma- pheochromocytoma (SDHA/B/C/D, SDHAF2) and, biallelic, mitochondrial complex II deficiency (Leigh syndrome, leukoencephalopathy, cardiomyopathy; SDHAF1).

Connections

sdh_assembly_factors -> sdh_holoenzyme Positively Regulates
SDHAF2-mediated FAD flavinylation of SDHA and SDHAF1-mediated Fe-S insertion into SDHB build the catalytic head that then assembles with the SDHC/SDHD membrane anchor into active Complex II.
Part 1: SDH holoenzyme (catalytic head + membrane anchor)
Succinate dehydrogenase holoenzyme (SDHA/SDHB/SDHC/SDHD)Protein Complexsdh_holoenzyme

Annotons

SDHA: FAD flavoprotein / succinate-oxidising subunit
sdha_activity
Participant: Family: SDHA / flavoprotein subunit family
Family:
SDHA / flavoprotein subunit familyPANTHER:PTHR11632
Representative Members: SDHA (human)UniProtKB:P31040

Function

succinate dehydrogenase activityGO:0000104
Substrates: succinate FAD (covalent cofactor)
Products: fumarate electrons transferred to the Fe-S wire (via FADH2)

Locations

mitochondrial matrixGO:0005759

FAD flavoprotein subunit; oxidises succinate to fumarate.

SDHB: iron-sulfur electron-transfer subunit
sdhb_activity
Participant: Family: SDHB / iron-sulfur subunit family
Family:
SDHB / iron-sulfur subunit familyPANTHER:PTHR11921
Representative Members: SDHB (human)UniProtKB:P21912

Function

electron transfer activityGO:0009055
Substrates: electrons from the FAD site
Products: electrons relayed through [2Fe-2S]/[4Fe-4S]/[3Fe-4S] clusters toward ubiquinone

Locations

mitochondrial matrixGO:0005759

Iron-sulfur electron-transfer subunit.

SDHC: heme-binding membrane anchor (large subunit)
sdhc_activity
Participant: Family: SDHC / cytochrome b large membrane-anchor family
Family:
SDHC / cytochrome b large membrane-anchor familyPANTHER:PTHR10978
Representative Members: SDHC (human)UniProtKB:Q99643

Function

heme bindingGO:0020037
Substrates: heme b ubiquinone
Products: ubiquinol (at the shared Q site with SDHD)

Locations

mitochondrial inner membraneGO:0005743

Heme-binding integral-membrane anchor subunit (cytochrome b560, large).

SDHD: heme-binding membrane anchor (small subunit)
sdhd_activity
Participant: Family: SDHD / cytochrome b small membrane-anchor family
Family:
SDHD / cytochrome b small membrane-anchor family
Representative Members: SDHD (human)UniProtKB:O14521

Function

heme bindingGO:0020037
Substrates: heme b ubiquinone
Products: ubiquinol (at the shared Q site with SDHC)

Locations

mitochondrial inner membraneGO:0005743

Heme-binding integral-membrane anchor subunit (cytochrome b small).

Part 2: SDH assembly factors (FAD flavinylation + Fe-S insertion)
SDH assembly factors (SDHAF2, SDHAF1)Reactionsdh_assembly_factors

Annotons

SDHAF2 (SDH5): SDHA flavinylation factor
sdhaf2_activity
Participant: Family: SDHAF2 / SDH5 (Sdh5) flavinylation-factor family
Family:
SDHAF2 / SDH5 (Sdh5) flavinylation-factor familyPANTHER:PTHR12469
Representative Members: SDHAF2 (human)UniProtKB:Q9NX18

Function

protein folding chaperoneGO:0044183
Substrates: SDHA apoprotein FAD
Products: covalently flavinylated SDHA (holo-flavoprotein)

Locations

mitochondrial matrixGO:0005759

Promotes covalent FAD attachment (flavinylation) of SDHA.

SDHAF1: SDHB Fe-S insertion factor
sdhaf1_activity
Participant: Family: SDHAF1 / LYR-motif Fe-S insertion-factor family
Family:
SDHAF1 / LYR-motif Fe-S insertion-factor familyPANTHER:PTHR47046
Representative Members: SDHAF1 (human)UniProtKB:A6NFY7

Function

protein-folding chaperone bindingGO:0051087
Substrates: HSC20 (HSCB) co-chaperone / Fe-S clusters
Products: Fe-S clusters inserted into SDHB

Locations

mitochondrial matrixGO:0005759

Delivers/inserts the iron-sulfur clusters into SDHB.