Yeast Vps13 promotes mitochondrial function and is localized at membrane contact sites.
The Vps13 protein family is highly conserved in eukaryotic cells. Mutations in human VPS13 genes result in a variety of diseases, such as chorea acanthocytosis (ChAc), but the cellular functions of Vps13 proteins are not well defined. In yeast, there is a single VPS13 orthologue, which is required for at least two different processes: protein sorting to the vacuole and sporulation. This study demonstrates that VPS13 is also important for mitochondrial integrity. In addition to preventing transfer of DNA from the mitochondrion to the nucleus, VPS13 suppresses mitophagy and functions in parallel with the endoplasmic reticulum-mitochondrion encounter structure (ERMES). In different growth conditions, Vps13 localizes to endosome-mitochondrion contacts and to the nuclear-vacuole junctions, indicating that Vps13 may function at membrane contact sites. The ability of VPS13 to compensate for the absence of ERMES correlates with its intracellular distribution. We propose that Vps13 is present at multiple membrane contact sites and that separation-of-function mutants are due to loss of Vps13 at specific junctions. Introduction of VPS13A mutations identified in ChAc patients at cognate sites in yeast VPS13 are specifically defective in compensating for the lack of ERMES, suggesting that mitochondrial dysfunction might be the basis for ChAc.
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215.
Jae-Sook
JS
Park
Department of Molecular Biology, University of Wyoming, Laramie, WY 82071.
Mary K
MK
Thorsness
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215.
Robert
R
Policastro
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215.
Luke L
LL
McGoldrick
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215.
Nancy M
NM
Hollingsworth
Department of Molecular Biology, University of Wyoming, Laramie, WY 82071.
Peter E
PE
Thorsness
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215 Aaron.neiman@stonybrook.edu.
Aaron M
AM
Neiman
D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D054546:Neuroacanthocytosis; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism
C089418:MMM1 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C110276:VPS13 protein, S cerevisiae; D033921:Vesicular Transport Proteins