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.

CHCHD2已在各种神经系统疾病（如帕金森氏病（PD），额颞痴呆（FTD）和阿尔茨海默氏病（AD））中发现了这种突变。它也是第一个突变导致PD的线粒体基因。CHCHD10是CHCHD2的同源物；与CHCHD2类似，已经在广泛的神经系统疾病（包括FTD和AD）中发现了CHCHD10的各种突变，其中在运动神经元疾病中发现的CHCHD10突变的频率很高。从功能上讲，CHCHD2和CHCHD10在线粒体中相互作用。最近的研究将CHCHD2的生物学功能与MICOS复合物（线粒体内膜组织系统）联系起来。多个实验模型表明，CHCHD2维持线粒体的ista裂，并且与疾病相关的CHCHD2突变以功能丧失的方式起作用。但是，CHCHD2和CHCHD10基因敲除小鼠模型在表型上看似正常，没有明显的线粒体缺陷。维持或增强线粒体cristae的策略可能提供纠正疾病状态下相关细胞缺陷的机会，并为CHCHD2相关的神经系统疾病揭示潜在的新靶标。