MITOCHONDRIAL DISULFIDE RELAY PROTEIN CHCHD4: KEY MOLECULE IN MITOCHONDRIAL REGULATION OF TUMORIGENESIS
AAKANSHA TOMAR
*
Transcriptional and Human Biology Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India.
*Author to whom correspondence should be addressed.
Abstract
Mitochondria plays an important role in the cellular response to the ever-changing tumor microenvironment. Several protein translocases in the mitochondria assist in the translocation of proteins into the mitochondria including some proteins with known roles in cancer. The increased translocation of these proteins results in an imbalance in mitochondrial protein biogenesis and homeostasis and modulate the cellular responses to stress and stimuli. Among these translocases, the role of CHCHD4 is imperative in unravelling the mitochondrial sensing considering its interactors and link to cancer signaling pathways as well as overexpression in various cancer settings. CHCHD4 in the intermembrane space is an important protein of the disulfide relay system which interacts with proteins of several cancer-critical pathways in response to the variable stresses like hypoxia and oxidative stress incurred upon the cell. This review will highlight the role of oxidoreductase CHCHD4 in regulating the import, folding and expression levels of proteins involved in tumor biology, that might be underlying the tumorigenic adaptation of cancerous cells. A better understanding of the role of CHCHD4 will further help in identifying and targeting pathways linked to tumorigenesis.
Keywords: Tumorigenesis, cancer biology, mitochondria, CHCHD4, p53, respiratory chain complex, intermembrane space, hypoxia.