Open AccessGas7 knockout affects PINK1 expression and mitochondrial dynamics in mouse cortical neurons
Author(s) -
Bhupana Jagannatham Naidu,
Huang BoTsang,
Liou GunnGuang,
Calkins Marcus J.,
LinChao Sue
Publication year - 2020
Publication title -
faseb bioadvances
Language(s) - English
Resource type - Journals
ISSN - 2573-9832
DOI - 10.1096/fba.2019-00091
Subject(s) - pink1 , mitochondrial fission , mitochondrion , microbiology and biotechnology , biology , dnaja3 , mitochondrial fusion , ectopic expression , mitophagy , mitochondrial dna , biochemistry , autophagy , apoptosis , cell culture , genetics , gene
Dynamic fission and fusion events regulate mitochondrial shape, distribution, and rejuvenation, and proper control of these processes is essential for neuronal homeostasis. Here, we report that Gas7, a known cytoskeleton regulator, controls mitochondrial dynamics within neurons of the central nervous system. In this study, we generated an improved Gas7 ‐knockout mouse and evaluated its mitochondrial phenotype. We first identified Gas7 in mitochondrial fractions from wild‐type brain tissue, and observed Gas7 colocalization with mitochondria in primary cortical neurons. In Gas7 ‐deficient brain tissue and neuronal cultures mitochondria were elongated with perinuclear clustering. These morphological abnormalities were associated with increased levels mitochondrial fusion proteins and increased PKA‐dependent phosphorylation of Drp‐1 in brain tissues, suggesting an imbalance of mitochondrial fusion and fission. Moreover, expression of mitochondrial quality control kinase, PINK1, and PINK1‐specific phosphorylation of Mfn‐2 (S442), Parkin (S65), and ubiquitin (S65) were all reduced in the knockout cells. Ectopic expression of Gas7 restored mitochondrial morphology and distribution, as well as PINK1 expression in Gas7 ‐null cortical neurons. Collectively, our results introduce a novel role of mouse Gas7 in determining the dynamics, morphology, and intracellular distribution of neuronal mitochondria, which are expected to be required for normal neuronal function.