MCU (CG18769) review notes

UniProt Q8IQ70 (Calcium uniporter protein, mitochondrial); PANTHER PTHR13462.

Literature journal

• Null allele abolishes fast uptake PMID:31042479; mild organismal phenotypes but short lifespan PMID:31042479
• EMRE dependence of fly MCU PMID:27099988; PMID:28726639.
• Gating residues conserved PMID:33296646 (fly MCU tested).
• Oxidative stress and ER-mitochondria transfer PMID:28726639.
• Memory PMID:27568554

Curation decisions (uniporter module, applied to MCU, EMRE, MICU1, MICU3, CG4704)

• GO:1990246 uniplex complex ACCEPTED for all subunits.
• GO:0006851 mitochondrial calcium ion transmembrane transport -> MODIFY to child GO:0036444 calcium import into the mitochondrion for all subunits.
• GO:0051560 mitochondrial calcium ion homeostasis ACCEPTED for all subunits.
• MCU uniporter activity (GO:0015292, a carrier-type term under secondary active transport) -> MODIFY to calcium channel activity.
• MF slots: MCU enables calcium channel activity; EMRE contributes_to calcium channel activity; MICU1/MICU3 calcium channel regulator activity; CG4704 calcium ion binding (untested paralog).

Deep research

MCU-deep-research-falcon.md (falcon) arrived after the review was first committed. It agrees with the review: MCU is the calcium-conducting channel subunit, not an enzyme or carrier, which supports replacing the carrier-type uniporter activity with calcium channel activity. It reports that the MCU52 null loses caffeine-evoked matrix calcium responses, which wild-type fly MCU restores and a DIME pore-motif mutant does not. No annotation decision changed.