2. Academic Validation
  3. Mitoguardin Regulates Mitochondrial Fusion through MitoPLD and Is Required for Neuronal Homeostasis

Mitoguardin Regulates Mitochondrial Fusion through MitoPLD and Is Required for Neuronal Homeostasis

  • Mol Cell. 2016 Jan 7;61(1):111-24. doi: 10.1016/j.molcel.2015.11.017.
Yongping Zhang 1,  Xiaoman Liu 1,  Jian Bai 1,  Xuejun Tian 1,  Xiaocui Zhao 1,  Wei Liu 1,  Xiuying Duan 1,  Weina Shang 1,  Heng-Yu Fan 1,  Chao Tong 2
Affiliations

Affiliations

  • 1 Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
  • 2 Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China. Electronic address: ctong@zju.edu.cn.
PMID: 26711011 DOI: 10.1016/j.molcel.2015.11.017
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.

Keywords

Drosophila; MitoPLD; mitochondrial fusion; neurodegeneration.

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