'Roles of a mitochondrial respiratory supercomplex assembly factor in muscle, fat and cancer metabolism' Satoshi Inoue

Speaker: Prof. Satoshi Inoue

Department of Anti-Aging Medicine, The University of Tokyo, Tokyo 113-8655, Japan

Dvision of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Japan

Title: Roles of a mitochondrial respiratory supercomplex assembly factor in muscle, fat and cancer metabolism

Abstract: Physiological energy production required for various cellular processes is mainly produced from mitochondrial respiratory chain that is comprised of multiple complexes. In particular, complexes I (NADH dehydrogenase), III (cytochrome c reductase), and IV (cytochrome c oxidase (COX)) are known to be assembled in macromolecular supercomplexes. Supercomplex formation has been considered as a necessary process to exert full activity of mitochondrial respiratory chain, yet little is known for the mechanism underlying the pathway. We isolated the cytochrome c oxidase subunit 7a related polypeptide (COX7RP) as an estrogen-inducible gene. We have clarified that COX7RP is an essential factor for the formation of mitochondrial respiratory supercomplexes by promoting the assembly of complexes III and IV with huge complex I. COX7RP plays an important role in muscle and bone metabolism. Cox7rp-knockout (Cox7rpKO) mice exhibit decreased endurance time in treadmill exercise due to the reduction of muscular COX activity. Cox7rpKO mice also exhibit a phenotype of impaired thermogenesis in response to cold exposure, indicating the reduced energy production in brown adipose tissue. On the other hand, we show that COX7RP promotes the growth of estrogen-dependent breast and endometrial cancer cells. siRNA targeted for COX7RP reduced in vivo tumor growth of breast and endometrial cancer cells. In addition, COX7RP mRNA level was elevated in some of the examined breast and endometrial cancer specimens. Thus, we assume that COX7RP will be critical for maintaining muscle strength as well as growth of breast and endometrial cancer by regulating mitochondria-dependent energy production.

Host: 

Open Technology Center

Cell Signal Unit