title: Caenorhabditis elegans mitofilin homologs control the morphology of mitochondrial cristae and influence reproduction and physiology.
abstract: 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.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Mun
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Lee
authors.forename: Ji Hui
authors.initials: JH
authors.lastname: Kim
authors.forename: Bum Ho
authors.initials: BH
authors.lastname: Yoo
authors.forename: Young Yil
authors.initials: YY
authors.lastname: Bahk
authors.forename: Hyeon-Sook
authors.initials: HS
authors.lastname: Koo
authors.forename: Sung Sik
authors.initials: SS
authors.lastname: Han
mesh_terms: 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
chemical_list: D029742:Caenorhabditis elegans Proteins; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D017382:Reactive Oxygen Species