2. Academic Validation
  3. PET117 assembly factor stabilizes translation activator TACO1 thereby upregulates mitochondria-encoded cytochrome C oxidase 1 synthesis

PET117 assembly factor stabilizes translation activator TACO1 thereby upregulates mitochondria-encoded cytochrome C oxidase 1 synthesis

  • Free Radic Biol Med. 2023 May 27;S0891-5849(23)00446-X. doi: 10.1016/j.freeradbiomed.2023.05.023.
Qiong Sun 1,  Le Shi 1,  Shuaijun Li 2,  Jialu Li 1,  Ruifen Zhang 1,  Xinghuai Huang 1,  Yongping Shao 3,  Zhihui Feng 3,  Yunhua Peng 1,  Zhiwei Yang 4,  Jiankang Liu 5,  Huadong Liu 6,  Jiangang Long 7
Affiliations

Affiliations

  • 1 Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.
  • 2 School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
  • 3 Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.
  • 4 MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, School of Physics, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.
  • 5 School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, Shandong, 266071, China.
  • 6 School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, Shandong, 266071, China. Electronic address: huadongliu@uor.edu.cn.
  • 7 Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China. Electronic address: jglong@xjtu.edu.cn.
PMID: 37247699 DOI: 10.1016/j.freeradbiomed.2023.05.023
Abstract

Cytochrome c oxidase, also known as complex IV, facilitates the transfer of electrons from cytochrome c to molecular oxygen, resulting in the production of ATP. The assembly of complex IV is a tightly regulated and intricate process that entails the coordinated synthesis and integration of subunits encoded by the mitochondria and nucleus into a functional complex. Accurate regulation of translation is crucial for maintaining proper mitochondrial function, and defects in this process can lead to a wide range of mitochondrial disorders and diseases. However, the mechanisms governing mRNA translation by mitoribosomes in mammals remain largely unknown. In this study, we elucidate the critical role of PET117, a chaperone protein involved in complex IV assembly, in the regulation of mitochondria-encoded cytochrome c oxidase 1 (COX1) protein synthesis in human cells. Depletion of PET117 reduced mitochondrial oxygen consumption rate and impaired mitochondrial function. PET117 was found to interact with and stabilize translational activator of COX1 (TACO1) and prevent its ubiquitination. TACO1 overexpression rescued the inhibitory effects on mitochondria caused by PET117 deficiency. These findings provide evidence for a novel PET117-TACO1 axis in the regulation of mitochondrial protein expression, and revealed a previously unknown role of PET117 in human cells.

Keywords

COX1; Mitochondrion; PET117; Protein stability; TACO1.

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