CHCHD2 mutations have been identified in various neurological diseases such as Parkinson’s disease (PD), frontotemporal dementia (FTD), and Alzheimer’s disease (AD). It is also the first mitochondrial gene whose mutations lead to PD. CHCHD10 is a homolog of CHCHD2; similar to CHCHD2, various mutations of CHCHD10 have been identified in a broad spectrum of neurological disorders, including FTD and AD, with a high frequency of CHCHD10 mutations found in motor neuron diseases. Functionally, CHCHD2 and CHCHD10 have been demonstrated to interact with each other in mitochondria. Recent studies link the biological functions of CHCHD2 to the MICOS complex (mitochondrial inner membrane organizing system). Multiple experimental models suggest that CHCHD2 maintains mitochondrial cristae and disease-associated CHCHD2 mutations function in a loss-of-function manner. However, both CHCHD2 and CHCHD10 knockout mouse models appear phenotypically normal, with no obvious mitochondrial defects. Strategies to maintain or enhance mitochondria cristae could provide opportunities to correct the associated cellular defects in disease state and unravel potential novel targets for CHCHD2-linked neurological conditions.
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