Twin CHCH Proteins, CHCHD2, and CHCHD10: Key Molecules of Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia

Int J Mol Sci. 2019 Feb 20;20(4):908. doi: 10.3390/ijms20040908.

Abstract

Mutations of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) and 10 (CHCHD10) have been found to be linked to Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and/or frontotemporal lobe dementia (FTD). CHCHD2 and CHCHD10 proteins, which are homologous proteins with 54% identity in amino acid sequence, belong to the mitochondrial coiled-coil-helix-coiled-coil-helix (CHCH) domain protein family. A series of studies reveals that these twin proteins form a multimodal complex, producing a variety of pathophysiology by the disease-causing variants of these proteins. In this review, we summarize the present knowledge about the physiological and pathological roles of twin proteins, CHCHD2 and CHCHD10, in neurodegenerative diseases.

Keywords: CHCH domain; MICOS; OXPHOS; coiled-coil-helix-coiled-coil-helix domain; mitochondria; neurodegenerative diseases; respiratory complexes.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / etiology*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Animals
  • DNA-Binding Proteins
  • Disease Susceptibility
  • Frontotemporal Dementia / etiology*
  • Frontotemporal Dementia / metabolism
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Mutation
  • Parkinson Disease / etiology*
  • Parkinson Disease / metabolism
  • Protein Binding
  • Protein Transport
  • Signal Transduction
  • Structure-Activity Relationship
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • CHCHD10 protein, human
  • CHCHD2 protein, human
  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • Transcription Factors