LETM1 notes

Deep research could not be generated (falcon HTTP 402; perplexity-lite unavailable;
openai key rejected). The review uses the cached literature and UniProt.

K+/H+ versus Ca2+/H+

• Original K+/H+ exchanger assignment, then a Ca2+/H+ proposal from a fly RNAi screen
  and liposome reconstitution [PMID:19797662 "Letm1 is a mitochondrial Ca2+/H+ antiporter"; PMID:24344246].
• In intact cells LETM1 does not set Ca2+ extrusion PMID:24898248.
• TMBIM5 is the mitochondrial Ca2+/H+ exchanger PMID:36321428.
• Patient variants abolish K+ efflux PMID:36055214.

Decision: K+/H+ antiport is the core activity; Ca2+/H+ antiport and calcium export were
marked as over-annotations (not removed, because reconstitution and PINK1
phosphorylation data, PMID:29123128, show a Ca2+ transport capacity in vitro).

Membrane organisation

LETM1 deforms proteoliposome membranes (PMID:32139798) and its knockdown causes swelling
and cristae disorganisation (PMID:18628306).