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Mitochondrial CHCHD2: Disease-Associated Mutations, Physiological Functions, and Current Animal Models.

Teresa R Kee1,2, Pamela Espinoza Gonzalez1, Jessica L Wehinger1

  • 1USF Health Byrd Alzheimer's Center and Research Institute, Tampa, FL, United States.

Frontiers in Aging Neuroscience
|May 10, 2021
PubMed
Summary

Rare mutations in the coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) protein are linked to Parkinson's disease. This review explores CHCHD2's function, mutations, and role in neurodegeneration.

Keywords:
CHCHD10CHCHD2Lewy body disordersParkinson’s diseasemitochondria

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Area of Science:

  • Mitochondrial biology
  • Neurogenetics
  • Cellular stress response

Background:

  • Rare mutations in coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) are associated with Parkinson's disease (PD) and Lewy body disorders.
  • CHCHD2 is a critical mitochondrial protein involved in oxidative phosphorylation and cellular stress responses.

Purpose of the Study:

  • To review CHCHD2 mutations in different populations.
  • To elucidate CHCHD2's physiological functions and role in α-synuclein pathology.
  • To discuss current animal models and the necessity of investigating CHCHD2 and CHCHD10 divergence.

Main Methods:

  • Literature review of CHCHD2 mutations, functions, and disease associations.
  • Analysis of CHCHD2's role in mitochondrial electron transport chain and hypoxic stress response.
  • Examination of CHCHD2's impact on α-synuclein pathology and cellular processes.

Main Results:

  • CHCHD2 mutations are found in Asian and Caucasian populations, linked to neurodegenerative diseases.
  • CHCHD2 regulates oxidative phosphorylation, nuclear transcription, cell migration, and apoptosis.
  • CHCHD2 mutations are implicated in α-synuclein pathology, a hallmark of PD.

Conclusions:

  • Understanding CHCHD2's diverse functions is crucial for neurodegenerative disease research.
  • Further investigation into CHCHD2 and CHCHD10 is needed to clarify their roles in distinct neurodegenerative conditions.
  • CHCHD2 represents a potential therapeutic target for Parkinson's disease and related disorders.