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Mitochondrial CHCHD-Containing Proteins: Physiologic Functions and Link with Neurodegenerative Diseases

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An Erratum to this article was published on 07 October 2016

This article has been updated

Abstract

The coiled-coil-helix-coiled-coil-helix domain (CHCHD)-containing proteins are evolutionarily conserved nucleus-encoded small mitochondrial proteins with important functions. So far, nine members have been identified in this protein family. All CHCHD proteins have at least one functional coiled-coil-helix-coiled-coil-helix (CHCH) domain, which is stabilized by two pairs of disulfide bonds between two helices. CHCHD proteins have various important pathophysiological roles in mitochondria and other key cellular processes. Mutations of CHCHD proteins have been associated with various human neurodegenerative diseases. Mutations of CHCHD10 are associated with amyotrophic lateral sclerosis (ALS) and/or frontotemporal lobe dementia (FTD), motor neuron disease, and late-onset spinal muscular atrophy and autosomal dominant mitochondrial myopathy. CHCHD10 stabilizes mitochondrial crista ultrastructure and maintains its integrity. In patients with CHCHD10 mutations, there are abnormal mitochondrial crista structure, deficiencies of respiratory chain complexes, impaired mitochondrial respiration, and multiple mitochondrial DNA (mtDNA) deletions. Recently, CHCHD2 mutations are linked with autosomal dominant and sporadic Parkinson’s disease (PD). The CHCHD2 is a multifunctional protein and plays roles in regulation of mitochondrial metabolism, synthesis of respiratory chain components, and modulation of cell apoptosis. With a better understanding of the pathophysiologic roles of CHCHD proteins, they may be potential novel therapeutic targets for human neurodegenerative diseases.

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Change history

  • 07 October 2016

    An erratum to this article has been published.

Abbreviations

ALS:

Amyotrophic lateral sclerosis

AD:

Alzheimer’s disease

CHCH:

Coiled-coil-helix-coiled-coil-helix

CHCHD:

Coiled-coil-helix-coiled-coil-helix domain

COX:

Cytochrome c oxidase

CPC:

Cysteine-proline-cysteine motif

DA:

Dopamine

EGFR:

Epidermal growth factor receptor

FTD:

Frontotemporal lobe dementia

GBA:

Guilt-by-association analysis

HPA:

Human Protein Atlas project

IMM:

The mitochondrial inner membrane

IMMD:

The autosomal dominant mitochondrial myopathy

IMS:

The mitochondrial intermembrane space

ISE:

The mitochondrial iron-sulfur exporter machinery

ITS:

The mitochondrial IMS-targeting signal

MICOS:

The mitochondrial contact site complex

MOMP:

The mitochondrial OMM permeabilization

mtDNA:

Mitochondrial DNA

MTS:

The mitochondrial targeting sequence

NSCLC:

Non-small-cell lung carcinoma

OMM:

The mitochondrial outer membrane

ORE:

Oxygen-responsive element

OxPhos:

The oxidative phosphorylation process

PD:

Parkinson’s disease

RBPJ:

The recombination signal sequence-binding protein Jκ

ROS:

Redox oxygen species

SMAJ:

The late-onset spinal muscular atrophy, Jokela type

tBID:

The truncated form of BID

WT:

Wild type

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Acknowledgments

We thank Singapore National Medical Research Council (STaR and Transition awards and clinical translational research programme in Parkinson’s disease) for their support.

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Authors and Affiliations

  1. National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore

    Zhi-Dong Zhou, Wuan-Ting Saw & Eng-King Tan

  2. Signature Research Program in Neuroscience and Behavioural Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore, 169857, Singapore

    Zhi-Dong Zhou & Eng-King Tan

  3. Department of Neurology, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore

    Eng-King Tan

Authors
  1. Zhi-Dong Zhou
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  2. Wuan-Ting Saw
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Correspondence to Zhi-Dong Zhou or Eng-King Tan.

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The authors declare that they have no competing interests.

Funding

This study is supported by Singapore National Medical Research Council (NMRC) grants including STaR and Transition awards and clinical translational research programme in Parkinson’s disease.

Additional information

Zhi-Dong Zhou and Wuan-Ting Saw contribute equally to this work

The original version of this article was revised: The reference citations on Table 2 were incorrect in both pdf and html. In the sentence “Furthermore, CHCHD3 is associated with the regulation of expression of an anti-apoptotic protein, BAG-1 [31].’’, reference citation [31] should be [15].’’

An erratum to this article is available at https://doi.org/10.1007/s12035-016-0160-4.

Electronic Supplementary Material

Supplementary Table 1

Predicted MTS fragment in CHCHD proteins (DOCX 15 kb)

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Zhou, ZD., Saw, WT. & Tan, EK. Mitochondrial CHCHD-Containing Proteins: Physiologic Functions and Link with Neurodegenerative Diseases. Mol Neurobiol 54, 5534–5546 (2017). https://doi.org/10.1007/s12035-016-0099-5

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