Chchd5, also known as CHTM1, is a mitochondrial protein involved in the oxidative folding process in the mitochondrial intermembrane space [1]. It is associated with pathways related to lipid metabolism, and its functions are crucial for maintaining normal cellular metabolism and may have implications for various physiological and pathological conditions.

A study on Chinese children found that the SNP rs3748024 in CHCHD5 is associated with systolic blood pressure (SBP), body mass index (BMI), obesity, and triglycerides, suggesting its role in hypertension and obesity-related processes [1]. In cancer research, CHTM1 (CHCHD5) deficiency in human cancer cells leads to defective lipid metabolism, poor growth under glucose/glutamine starvation, and sensitizes cells to metabolic stress-induced cell death. CHTM1 interacts with Apoptosis Inducing Factor 1 (AIF1) and negatively regulates AIF1-mediated caspase-independent cell death, with p38 kinase playing a critical role in this process. Also, CHTM1 levels are increased in the majority of lung tumors compared to normal tissues [2].

In conclusion, Chchd5 is essential for mitochondrial-related oxidative folding and cellular metabolism. Studies on its genetic variants and loss-of-function effects in different models have revealed its potential roles in diseases such as hypertension, obesity, and cancer, highlighting its importance in understanding the mechanisms underlying these conditions.

References:

1. Wu, Lijun, Gao, Liwang, Zhao, Xiaoyuan, Wu, Jianxin, Mi, Jie. 2017. A new risk locus in CHCHD5 for hypertension and obesity in a Chinese child population: a cohort study. In BMJ open, 7, e016241. doi:10.1136/bmjopen-2017-016241. https://pubmed.ncbi.nlm.nih.gov/28893745/

2. Babbar, Mansi, Huang, Ying, Curtiss, Christopher M, Sheikh, M Saeed. 2019. CHTM1 regulates cancer cell sensitivity to metabolic stress via p38-AIF1 pathway. In Journal of experimental & clinical cancer research : CR, 38, 271. doi:10.1186/s13046-019-1253-5. https://pubmed.ncbi.nlm.nih.gov/31221176/