Caenorhabditis elegans mitofilin homologs control the morphology of mitochondrial cristae and influence reproduction and physiology.
Human mitofilin is a mitochondrial protein that controls cristae formation. Here, we investigated the role of the Caenorhabditis elegans mitofilin homologs, IMMT-1 and -2, in reproduction, physiology, and mitochondrial cristae formation. Mutation of either immt-1 or immt-2 produced defects in germline development and egg-laying. These defects were exacerbated by the double mutation, which greatly reduced motility, increased levels of reactive oxygen species, decreased mitochondrial mass, and imparted resistance to oxidative stress. Cryo-electron microscopy and electron tomography revealed that each of the single mutations resulted in curved and stacked mitochondrial crista tubules as well as a reduced number of crista junctions. The immt-2 mutation was also associated with the presence of outer mitochondrial membrane pores, which were larger in the double mutant. IMMT-1 and IMMT-2 proteins were localized to the inner mitochondrial membrane, as seen by immunoelectron microscopy, and they behaved as oligomers or large complexes with F(1)F(0) ATP synthase in native polyacrylamide gel electrophoresis. These findings suggest that the two C. elegans mitofilin isoforms have non-overlapping functions in controlling mitochondrial cristae formation.
Mun
Ji Young
JY
School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Lee
Tae Hoon
TH
Kim
Ji Hui
JH
Yoo
Bum Ho
BH
Bahk
Young Yil
YY
Koo
Hyeon-Sook
HS
Han
Sung Sik
SS
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D017382:Reactive Oxygen Species