Abstract

Mitochondria are dynamic organelles that undergo fusion and fission in response to various physiological and stress stimuli, which play key roles in diverse mitochondrial functions such as energy metabolism, intracellular signaling, and apoptosis. OPA1, a mitochondrial dynamin-like GTPase, is responsible for the inner membrane fusion of mitochondria, and the function of OPA1 is regulated by proteolytic cleavage in response to various metabolic stresses. Growing evidences highlighted the importance of mitochondrial adaptation in response to metabolic stimuli. Here, we demonstrated the role of p32/C1QBP in mitochondrial morphology by regulating OMA1-dependent proteolytic processing of OPA1. Genetic ablation of p32/C1QBP activates OMA1, cleaves OPA1, and leads mitochondrial fragmentation and swelling. The loss of p32/C1QBP decreased mitochondrial respiration and lipid utilization, sensitized cells to mitochondrial stress, and triggered a metabolic shift from oxidative phosphorylation to glycolysis, which were correlated with apoptosis in cancer cells and the inhibition of 3D-spheroid formation. These results suggest a unique regulation of cell physiology by mitochondria and provide a basis for a new therapeutic strategy for cancer.

Details

Title
p32/C1QBP regulates OMA1-dependent proteolytic processing of OPA1 to maintain mitochondrial connectivity related to mitochondrial dysfunction and apoptosis
Author
Noh Solhee 1 ; Sophors, Phorl 1 ; Naskar Rema 1 ; Kakada, Oeum 1 ; Seo, Yuri 1 ; Kim, Eunjung 1 ; Hee-Seok, Kweon 2 ; Joo-Yong, Lee 3 

 Chungnam National University, Graduate School of Analytical Science and Technology (GRAST), Taejon, Republic of Korea (GRID:grid.254230.2) (ISNI:0000 0001 0722 6377) 
 Korea Basic Science Institute, Center for Research Equipment, Cheongju, Korea (GRID:grid.410885.0) (ISNI:0000 0000 9149 5707) 
 Chungnam National University, Graduate School of Analytical Science and Technology (GRAST), Taejon, Republic of Korea (GRID:grid.254230.2) (ISNI:0000 0001 0722 6377); Korea Basic Science Institute, Taejon, Republic of Korea (GRID:grid.410885.0) (ISNI:0000 0000 9149 5707) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2418885360
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.