title: Mitoguardin Regulates Mitochondrial Fusion through MitoPLD and Is Required for Neuronal Homeostasis.
abstract: Mitochondria undergo frequent morphological changes through fission and fusion. Mutations in core members of the mitochondrial fission/fusion machinery are responsible for severe neurodegenerative diseases. However, the mitochondrial fission/fusion mechanisms are poorly understood. We found that the loss of a mitochondrial protein encoding gene, mitoguardin (miga), leads to mitochondrial defects and neurodegeneration in fly eyes. Mammals express two orthologs of miga: Miga1 and Miga2. Both MIGA1 and MIGA2 form homotypic and heterotypic complexes on the outer membrane of the mitochondria. Loss of MIGA results in fragmented mitochondria, whereas overexpression of MIGA leads to clustering and fusion of mitochondria in both fly and mammalian cells. MIGA proteins function downstream of mitofusin and interact with MitoPLD to stabilize MitoPLD and facilitate MitoPLD dimer formation. Therefore, we propose that MIGA proteins promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD.
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Liu
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Bai
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Tian
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Duan
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Shang
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Heng-Yu
authors.initials: HY
authors.lastname: Fan
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China. Electronic address: ctong@zju.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Tong
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases; D005260:Female; D005838:Genotype; D057809:HEK293 Cells; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology* / Q000473:pathology; D063154:Mitochondrial Dynamics; D051336:Mitochondrial Membranes / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D041681:NIH 3T3 Cells; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D010641:Phenotype; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000201:enzymology; D055503:Protein Multimerization; D034622:RNA Interference; D014162:Transfection
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000612422:mitoguardin-1 protein, mouse; D004722:Endoribonucleases; C521347:Zuc protein, Drosophila; D010739:Phospholipase D; C000607813:mitoPLD protein, human; C558126:mitoPLD protein, mouse
keywords: Drosophila; MitoPLD; mitochondrial fusion; neurodegeneration