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Loss of Parkinson’s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c
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Loss of Parkinson’s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c
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Journal Article
Loss of Parkinson’s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c
2017
Overview
Mutations in
CHCHD2
have been identified in some Parkinson’s disease (PD) cases. To understand the physiological and pathological roles of CHCHD2, we manipulated the expression of CHCHD2 in
Drosophila
and mammalian cells. The loss of CHCHD2 in
Drosophila
causes abnormal matrix structures and impaired oxygen respiration in mitochondria, leading to oxidative stress, dopaminergic neuron loss and motor dysfunction with age. These PD-associated phenotypes are rescued by the overexpression of the translation inhibitor 4E-BP and by the introduction of human CHCHD2 but not its PD-associated mutants. CHCHD2 is upregulated by various mitochondrial stresses, including the destabilization of mitochondrial genomes and unfolded protein stress, in
Drosophila
. CHCHD2 binds to cytochrome
c
along with a member of the Bax inhibitor-1 superfamily, MICS1, and modulated cell death signalling, suggesting that CHCHD2 dynamically regulates the functions of cytochrome
c
in both oxidative phosphorylation and cell death in response to mitochondrial stress.
Mutations in
CHCHD2
are associated with Parkinson’s disease. Here the authors investigate the physiological and pathological roles of CHCHD2 in
Drosophila
and mammalian cells, and find that it regulates mitochondrial respiration through stabilizing cytochrome c.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 64
/ 64/24
/ 82
/ 82/1
/ 82/29
/ 96
/ 96/95
/ Adaptor Proteins, Signal Transducing - metabolism
/ Animals
/ Disease
/ Dopaminergic Neurons - metabolism
/ Dopaminergic Neurons - pathology
/ Drosophila melanogaster - metabolism
/ Drosophila melanogaster - ultrastructure
/ Drosophila Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Insects
/ Male
/ Medicine
/ Mice
/ Mitochondria - ultrastructure
/ Mitochondrial Proteins - metabolism
/ Mutation
/ Nerve Degeneration - pathology
/ Neurons
/ Parkinson Disease - genetics
/ Parkinson Disease - pathology
/ Proteins
/ Science
/ Transcription Factors - metabolism
