Molecular Neurobiology

, Volume 54, Issue 7, pp 5534–5546 | Cite as

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

  • Zhi-Dong Zhou
  • Wuan-Ting Saw
  • Eng-King Tan


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.


Apoptosis Coiled-coil-helix-coiled-coil-helix domain proteins Mitochondria Mitochondrial cristae Neurodegenerative disease 



Amyotrophic lateral sclerosis


Alzheimer’s disease




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


Cytochrome c oxidase


Cysteine-proline-cysteine motif




Epidermal growth factor receptor


Frontotemporal lobe dementia


Guilt-by-association analysis


Human Protein Atlas project


The mitochondrial inner membrane


The autosomal dominant mitochondrial myopathy


The mitochondrial intermembrane space


The mitochondrial iron-sulfur exporter machinery


The mitochondrial IMS-targeting signal


The mitochondrial contact site complex


The mitochondrial OMM permeabilization


Mitochondrial DNA


The mitochondrial targeting sequence


Non-small-cell lung carcinoma


The mitochondrial outer membrane


Oxygen-responsive element


The oxidative phosphorylation process


Parkinson’s disease


The recombination signal sequence-binding protein Jκ


Redox oxygen species


The late-onset spinal muscular atrophy, Jokela type


The truncated form of BID


Wild type



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

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no competing interests.


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.

Supplementary material

12035_2016_99_MOESM1_ESM.docx (16 kb)
Supplementary Table 1 Predicted MTS fragment in CHCHD proteins (DOCX 15 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.National Neuroscience Institute of SingaporeSingaporeSingapore
  2. 2.Signature Research Program in Neuroscience and Behavioural DisordersDuke-NUS Graduate Medical School SingaporeSingaporeSingapore
  3. 3.Department of NeurologySingapore General HospitalSingaporeSingapore

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