TMEM70 facilitates biogenesis of mammalian ATP synthase by promoting subunit c incorporation into the rotor structure of the enzyme

0520774 - FGÚ 2020 RIV US eng J - Journal Article
Kovalčíková, Jana - Vrbacký, Marek - Pecina, Petr - Tauchmannová, Kateřina - Nůsková, Hana - Kaplanová, Vilma - Brázdová, Andrea - Alán, Lukáš - Eliáš, Jan - Čunátová, Kristýna - Kořínek, Vladimír - Sedláček, Radislav - Mráček, Tomáš - Houštěk, Josef
TMEM70 facilitates biogenesis of mammalian ATP synthase by promoting subunit c incorporation into the rotor structure of the enzyme.
FASEB Journal. Roč. 33, č. 12 (2019), s. 14103-14117. ISSN 0892-6638. E-ISSN 1530-6860
R&D Projects: GA ČR(CZ) GB14-36804G; GA MZd(CZ) NV16-33018A; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT ED2.1.00/19.0395
Institutional support: RVO:67985823 ; RVO:68378050
Keywords : mouse knockout * mitochondria * ancillary factor * ATP5G assembly
OECD category: Genetics and heredity (medical genetics to be 3)
Impact factor: 4.966, year: 2019
Method of publishing: Limited access
https://doi.org/10.1096/fj.201900685RR

Biogenesis of F1Fo ATP synthase depends on TMEM70 protein, localized in the inner mitochondrial membrane of higher eukaryotes. TMEM70 absence causes severe ATP synthase deficiency and leads to a neonatal mitochondrial encephalo-cardiomyopathy in humans. However, the exact biochemical function of TMEM70 remains unknown. Using TMEM70 conditional knockout in mice we show that absence of TMEM70 impairs the early stage of enzyme biogenesis by preventing incorporation of hydrophobic subunit c into rotor structure of the enzyme. This results in formation of an incomplete, pathological enzyme complex lacking Fo proton channel composed of subunits c and a. We demonstrated direct interaction between TMEM70 and subunit c and showed that overexpression of subunit c in TMEM70‐/‐ cells partially rescued TMEM70 defect. Accordingly, TMEM70 knockdown prevented subunit c accumulation otherwise observed in F1‐deficient cells. Altogether, we identified TMEM70 as specific ancillary factor for subunit c.
Permanent Link: http://hdl.handle.net/11104/0305447