Mitochondrial membrane assembly of TMEM70 protein

TMEM70 forms oligomeric scaffolds within mitochondrial cristae promotingin situassembly of mammalian ATP synthase proton channel

“…These results indicate that TMEM70 is an integral protein of the inner membrane with domains exposed to the intermembrane space. Altogether, these data led us to propose a topological model for TMEM70 (Fig.1E) in agreement with previous studies (Jonckheere et al , 2011; Kratochvílová et al , 2014).…”

“…To define the location and topology of TMEM70, we performed cell fractionation experiments, using specific protein markers of different subcellular compartments (Fig.1B). Endogenous TMEM70 was detected almost exclusively in the crude mitochondrial fraction and a very similar profile was obtained for the ATP synthase subunit Beta confirming the mitochondrial subcellular localization of TMEM70 established previously (Hejzlarová et al , 2011; Jonckheere et al , 2011; Kratochvílová et al , 2014). We obtained similar results with transduced cells in which TMEM70 is overexpressed, which ruled out mistargeting and mislocalization of exogenous TMEM70 (Supp Fig.2).…”

A dual function of TMEM70 in OXPHOS: assembly of complexes I and V

“…in human TMEM70-TMEM186: 14%, TMEM70-TMEM223: 9%, TMEM186-TMEM223: 15%), in silico predictions indicate a similar asymmetric hairpin topology for all three proteins; a short N-terminal sequence located in the mitochondrial matrix followed by an in/out and an out/in transmembrane helix and a longer C-terminal sequence (Supplementary Fig. S10), consistent with the experimental results for TMEM70 17 . Furthermore, also the Saccharomyces cerevisiae protein Mrx15, that is homologous to the TMEM70/186/223 family and within this family most similar to TMEM223 (E=8e-28, 10% identity), has this asymmetric hairpin topology 37 .…”

“…TMEM70 is a transmembrane protein that localizes in the inner membrane of the mitochondria 15,16 . It contains two transmembrane regions that form a hairpin structure of which the N- and C-termini are located in the mitochondrial matrix 17 . Mutations in TMEM70 have been reported to severely diminish the content of CV in a large cohort of patients 14,18-26 , and of all nuclear encoded proteins affecting CV, TMEM70 is the most commonly mutated in disease 27 .…”

TMEM70 deficiency: long‐term outcome of 48 patients

“…TMEM70 is an important factor for the biogenesis and stabilisation of ATP synthase, but its exact role still needs to be determined (Torraco et al 2012;Hejzlarová et al 2011). Recently, the protein structure has been demonstrated (Kratochvílová et al 2014).…”