The presence of disulfide bonds reveals an evolutionarily conserved mechanism involved in mitochondrial protein translocase assembly.
Disulfide bond formation is crucial for the biogenesis and structure of many proteins that are localized in the intermembrane space of mitochondria. The importance of disulfide bond formation within mitochondrial proteins was extended beyond soluble intermembrane space proteins. Tim22, a membrane protein and core component of the mitochondrial translocase TIM22, forms an intramolecular disulfide bond in yeast. Tim22 belongs to the Tim17/Tim22/Tim23 family of protein translocases. Here, we present evidence of the high evolutionary conservation of disulfide bond formation in Tim17 and Tim22 among fungi and metazoa. Topological models are proposed that include the location of disulfide bonds relative to the predicted transmembrane regions. Yeast and human Tim22 variants that are not oxidized do not properly integrate into the membrane complex. Moreover, the lack of Tim17 oxidation disrupts the TIM23 translocase complex. This underlines the importance of disulfide bond formation for mature translocase assembly through membrane stabilization of weak transmembrane domains.
International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.|Department of Microbiology, Monash University, Melbourne, Victoria 3800, Australia.
Lidia
L
Wrobel
International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
Anna M
AM
Sokol
International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
Magdalena
M
Chojnacka
International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
Agnieszka
A
Chacinska
D005075:Biological Evolution; D004220:Disulfides / Q000737:chemistry*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D004220:Disulfides; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins