Mitochondrial inner membrane protein MPV17 (MPV17)

Mitochondrial inner membrane protein MPV17 (MPV17) is an integral membrane protein predominantly localized to the inner membrane of mitochondria. It adopts a compact structure with six transmembrane α-helices and oligomerizes, forming non-selective channels within the membrane that are voltage, pH, and redox sensitive. MPV17 is crucial for maintaining mitochondrial DNA (mtDNA) integrity, mitochondrial nucleotide pools, and redox balance. Its deficiency or pathogenic mutations induce severe, tissue-specific mtDNA depletion syndromes that manifest with infantile-onset liver dysfunction and neurologic deficits, sometimes extending to multisystem failure. Disease-causing mutations affect protein folding, channel function, and oligomerization, resulting in energy failure of the affected tissues. MPV17 interacts with proteins critical to mitochondrial structure and function—including ATP synthase, Cyclophilin D, MIC60, and GRP75—modulating cristae morphology and calcium homeostasis especially under cellular stress. Despite its crucial function, MPV17 remains poorly understood at the structural and mechanistic level, and no drugs are currently reported to target this protein directly. Its clinical significance is clear for diagnostic purposes; targeted therapeutic strategies are challenged by the protein’s essential, context-dependent mitochondrial role and risk of mitochondrial dysfunction.

Other names

Protein Mpv17SYM1 (in yeast)Mitochondrial inner membrane protein Mpv17MPV17 geneMpv17Human homolog of glomerulosclerosis and nephrotic syndromeGlomerulosclerosis (context: disease link)MTDPS6 (mitochondrial DNA depletion syndrome 6)CMT2EE (Charcot-Marie-Tooth disease type 2EE; rare)MpV17 mitochondrial inner membrane protein

Not applicable; no documented drugs with defined mechanism of action acting directly on MPV17.