RRC ID 70765
著者 Shen JL, Fortier TM, Zhao YG, Wang R, Burmeister M, Baehrecke EH.
タイトル Vmp1, Vps13D, and Marf/Mfn2 function in a conserved pathway to regulate mitochondria and ER contact in development and disease.
ジャーナル Curr Biol
Abstract Mutations in Vps13D cause defects in autophagy, clearance of mitochondria, and human movement disorders. Here, we discover that Vps13D functions in a pathway downstream of Vmp1 and upstream of Marf/Mfn2. Like vps13d, vmp1 mutant cells exhibit defects in autophagy, mitochondrial size, and clearance. Through the relationship between vmp1 and vps13d, we reveal a novel role for Vps13D in the regulation of mitochondria and endoplasmic reticulum (ER) contact. Significantly, the function of Vps13D in mitochondria and ER contact is conserved between fly and human cells, including fibroblasts derived from patients suffering from VPS13D mutation-associated neurological symptoms. vps13d mutants have increased levels of Marf/MFN2, a regulator of mitochondrial fusion. Importantly, loss of marf/MFN2 suppresses vps13d mutant phenotypes, including mitochondria and ER contact. These findings indicate that Vps13d functions at a regulatory point between mitochondria and ER contact, mitochondrial fusion and autophagy, and help to explain how Vps13D contributes to disease.
巻・号 31(14)
ページ 3028-3039.e7
公開日 2021-7-26
DOI 10.1016/j.cub.2021.04.062
PII S0960-9822(21)00609-6
PMID 34019822
PMC PMC8319081
MeSH Autophagy / genetics Endoplasmic Reticulum* / metabolism GTP Phosphohydrolases / metabolism Humans Membrane Proteins / genetics Membrane Proteins / metabolism Mitochondria* / metabolism Mitochondrial Dynamics / genetics Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism Mitochondrial Size Proteins / metabolism
IF 9.601
リソース情報
ショウジョウバエ DGRC#112001