Mitochondrial nucleoid condensates drive peripheral fission through high membrane curvature

Qixin Chen; Liu-Yi Liu; Zhiqi Tian; Zhou Fang; Kang-Nan Wang; Xintian Shao; Chengying Zhang; Weiwei Zou; Fiona Rowan; Kangqiang Qiu; Baohua Ji; Jun-Lin Guan; Dechang Li; Zong-Wan Mao; Jiajie Diao

doi:10.1016/j.celrep.2023.113472

Mitochondrial nucleoid condensates drive peripheral fission through high membrane curvature

Cell Rep. 2023 Dec 26;42(12):113472. doi: 10.1016/j.celrep.2023.113472. Epub 2023 Nov 24.

Authors

Qixin Chen¹, Liu-Yi Liu², Zhiqi Tian³, Zhou Fang⁴, Kang-Nan Wang², Xintian Shao³, Chengying Zhang³, Weiwei Zou⁵, Fiona Rowan³, Kangqiang Qiu³, Baohua Ji⁴, Jun-Lin Guan³, Dechang Li⁶, Zong-Wan Mao⁷, Jiajie Diao⁸

Affiliations

¹ Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. Electronic address: chenqixin@sdfmu.edu.cn.
² MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, IGCME, GBRCE for Functional Molecular Engineering, Guangzhou 510275, China.
³ Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
⁴ Institute of Biomechanics and Applications, Department of Engineering Mechanics, Zhejiang University, Hangzhou 310027, China.
⁵ Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
⁶ Institute of Biomechanics and Applications, Department of Engineering Mechanics, Zhejiang University, Hangzhou 310027, China. Electronic address: dcli@zju.edu.cn.
⁷ MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, IGCME, GBRCE for Functional Molecular Engineering, Guangzhou 510275, China. Electronic address: cesmzw@mail.sysu.edu.cn.
⁸ Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. Electronic address: jiajie.diao@uc.edu.

PMID: 37999975
DOI: 10.1016/j.celrep.2023.113472

Abstract

Mitochondria are dynamic organelles that undergo fusion and fission events, in which the mitochondrial membrane and DNA (mtDNA) play critical roles. The spatiotemporal organization of mtDNA reflects and impacts mitochondrial dynamics. Herein, to study the detailed dynamics of mitochondrial membrane and mtDNA, we rationally develop a dual-color fluorescent probe, mtGLP, that could be used for simultaneously monitoring mitochondrial membrane and mtDNA dynamics via separate color outputs. By combining mtGLP with structured illumination microscopy to monitor mitochondrial dynamics, we discover the formation of nucleoid condensates in damaged mitochondria. We further reveal that nucleoid condensates promoted the peripheral fission of damaged mitochondria via asymmetric segregation. Through simulations, we find that the peripheral fission events occurred when the nucleoid condensates interacted with the highly curved membrane regions at the two ends of the mitochondria. Overall, we show that mitochondrial nucleoid condensates utilize peripheral fission to maintain mitochondrial homeostasis.

Keywords: CP: Cell biology; chemical biology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA, Mitochondrial* / genetics
Mitochondria* / genetics
Mitochondrial Dynamics / genetics
Mitochondrial Membranes
Mitochondrial Proteins

Substances

DNA, Mitochondrial
Mitochondrial Proteins