Promotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults

Koichi Hasegawa (), Toru Yasuda, Chinatsu Shiraishi, Kazushiro Fujiwara, Serge Przedborski, Hideki Mochizuki and Kazuaki Yoshikawa ()
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Koichi Hasegawa: Laboratory of Regulation of Neuronal Development, Institute for Protein Research, Osaka University
Toru Yasuda: Graduate School of Medicine, Osaka University
Chinatsu Shiraishi: Laboratory of Regulation of Neuronal Development, Institute for Protein Research, Osaka University
Kazushiro Fujiwara: Laboratory of Regulation of Neuronal Development, Institute for Protein Research, Osaka University
Serge Przedborski: Pathology and Cell Biology, Columbia University
Hideki Mochizuki: Graduate School of Medicine, Osaka University
Kazuaki Yoshikawa: Laboratory of Regulation of Neuronal Development, Institute for Protein Research, Osaka University

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract Neurons rely heavily on mitochondria for their function and survival. Mitochondrial dysfunction contributes to the pathogenesis of neurodegenerative diseases such as Parkinson’s disease. PGC-1α is a master regulator of mitochondrial biogenesis and function. Here we identify necdin as a potent PGC-1α stabilizer that promotes mitochondrial biogenesis via PGC-1α in mammalian neurons. Expression of genes encoding mitochondria-specific proteins decreases significantly in necdin-null cortical neurons, where mitochondrial function and expression of the PGC-1α protein are reduced. Necdin strongly stabilizes PGC-1α by inhibiting its ubiquitin-dependent degradation. Forced expression of necdin enhances mitochondrial function in primary cortical neurons and human SH-SY5Y neuroblastoma cells to prevent mitochondrial respiratory chain inhibitor-induced degeneration. Moreover, overexpression of necdin in the substantia nigra in vivo of adult mice protects dopaminergic neurons against degeneration in experimental Parkinson’s disease. These data reveal that necdin promotes mitochondrial biogenesis through stabilization of endogenous PGC-1α to exert neuroprotection against mitochondrial insults.

Date: 2016
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DOI: 10.1038/ncomms10943

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