Cardiolipin's propensity for phase transition and its reorganization by dynamin-related protein 1 form a basis for mitochondrial membrane fission

被引:126
作者
Stepanyants, Natalia [1 ]
Macdonald, Patrick J. [1 ]
Francy, Christopher A. [2 ,3 ,4 ]
Mears, Jason A. [2 ,3 ,4 ]
Qi, Xin [1 ,2 ]
Ramachandran, Rajesh [1 ,4 ]
机构
[1] Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Sch Med, Ctr Mitochondrial Dis, Cleveland, OH 44106 USA
[3] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA
[4] Case Western Reserve Univ, Sch Med, Cleveland Ctr Membrane & Struct Biol, Cleveland, OH 44106 USA
基金
美国国家卫生研究院;
关键词
CONFORMATIONAL-CHANGES; GTPASE ACTIVITY; BARTH-SYNDROME; DOMAIN; LIPIDS; DIVISION; FUSION; MICRODOMAINS; LAMELLAR; OLIGOMERIZATION;
D O I
10.1091/mbc.E15-06-0330
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cardiolipin (CL) is an atypical, dimeric phospholipid essential for mitochondrial dynamics in eukaryotic cells. Dynamin-related protein 1 (Drp1), a cytosolic member of the dynamin superfamily of large GTPases, interacts with CL and functions to sustain the balance of mitochondrial division and fusion by catalyzing mitochondrial fission. Although recent studies have indicated a role for CL in stimulating Drp1 self-assembly and GTPase activity at the membrane surface, the mechanism by which CL functions in membrane fission, if at all, remains unclear. Here, using a variety of fluorescence spectroscopic and imaging approaches together with model membranes, we demonstrate that Drp1 and CL function cooperatively in effecting membrane constriction toward fission in three distinct steps. These involve 1) the preferential association of Drp1 with CL localized at a high spatial density in the membrane bilayer, 2) the reorganization of unconstrained, fluid-phase CL molecules in concert with Drp1 self-assembly, and 3) the increased propensity of CL to transition from a lamellar, bilayer arrangement to an inverted hexagonal, nonbilayer configuration in the presence of Drp1 and GTP, resulting in the creation of localized membrane constrictions that are primed for fission. Thus we propose that Drp1 and CL function in concert to catalyze mitochondrial division.
引用
收藏
页码:3104 / 3116
页数:13
相关论文
共 49 条
[31]   Membrane Remodeling Induced by the Dynamin-Related Protein Drp1 Stimulates Bax Oligomerization [J].
Montessuit, Sylvie ;
Somasekharan, Syam Prakash ;
Terrones, Oihana ;
Lucken-Ardjomande, Safa ;
Herzig, Sebastien ;
Schwarzenbacher, Robert ;
Manstein, Dietmar J. ;
Bossy-Wetzel, Ella ;
Basanez, Gorka ;
Meda, Paolo ;
Martinou, Jean-Claude .
CELL, 2010, 142 (06) :889-901
[32]   Targeting an allosteric site in dynamin-related protein 1 to inhibit Fis1-mediated mitochondrial dysfunction [J].
Rios, Luis ;
Pokhrel, Suman ;
Li, Sin-Jin ;
Heo, Gwangbeom ;
Haileselassie, Bereketeab ;
Mochly-Rosen, Daria .
NATURE COMMUNICATIONS, 2023, 14 (01)
[33]   High glucose concentration abrogates sevoflurane post-conditioning cardioprotection by advancing mitochondrial fission but dynamin-related protein 1 inhibitor restores these effects [J].
Yu, J. ;
Maimaitili, Y. ;
Xie, P. ;
Wu, J. J. ;
Wang, J. ;
Yang, Y. N. ;
Ma, H. P. ;
Zheng, H. .
ACTA PHYSIOLOGICA, 2017, 220 (01) :83-98
[34]   Role of dynamin-related protein 1-mediated mitochondrial fission in resistance of mouse C2C12 myoblasts to heat injury [J].
Yu, Tianzheng ;
Deuster, Patricia ;
Chen, Yifan .
JOURNAL OF PHYSIOLOGY-LONDON, 2016, 594 (24) :7419-7433
[35]   Novel insight into mitochondrial dynamin-related protein-1 as a new chemo-sensitizing target in resistant cancer cells [J].
Alkafaas, Samar Sami ;
Obeid, Omar K. ;
Radwan, Mustafa Ali ;
Elsalahaty, Mohamed I. ;
ElKafas, Sara Samy ;
Hafez, Wael ;
Jankovic, Nenad ;
Hessien, Mohamed .
BIOORGANIC CHEMISTRY, 2024, 150
[36]   Rotaviral nonstructural protein 4 triggers dynamin-related protein 1-dependent mitochondrial fragmentation during infection [J].
Mukherjee, Arpita ;
Patra, Upayan ;
Bhowmick, Rahul ;
Chawla-Sarkar, Mamta .
CELLULAR MICROBIOLOGY, 2018, 20 (06)
[37]   Dynamin-related protein 1 regulates substrate oxidation in skeletal muscle by stabilizing cellular and mitochondrial calcium dynamics [J].
King, William T. ;
Axelrod, Christopher L. ;
Zunica, Elizabeth R. M. ;
Noland, Robert C. ;
Davuluri, Gangarao ;
Fujioka, Hisashi ;
Tandler, Bernard ;
Pergola, Kathryn ;
Hermann, Gerlinda E. ;
Rogers, Richard C. ;
Lopez-Domenech, Sandra ;
Dantas, Wagner S. ;
Stadler, Krisztian ;
Hoppel, Charles L. ;
Kirwan, John P. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2021, 297 (04)
[38]   The intramitochondrial dynamin-related GTPase, Mgm1p, is a component of a protein complex that mediates mitochondrial fusion [J].
Wong, ED ;
Wagner, JA ;
Scott, SV ;
Okreglak, V ;
Holewinske, TJ ;
Cassidy-Stone, A ;
Nunnari, J .
JOURNAL OF CELL BIOLOGY, 2003, 160 (03) :303-311
[39]   Dynamin-related protein 1 is a critical regulator of mitochondrial calcium homeostasis during myocardial ischemia/reperfusion injury [J].
Piao, Lin ;
Fang, Yong-Hu ;
Fisher, Michael ;
Hamanaka, Robert B. ;
Ousta, Alaa ;
Wu, Rongxu ;
Mutlu, Goekhan M. ;
Garcia, Alfredo J. ;
Archer, Stephen L. ;
Sharp, Willard W. .
FASEB JOURNAL, 2024, 38 (01)
[40]   Estrogen Regulates Mitochondrial Morphology through Phosphorylation of Dynamin-related Protein 1 in MCF7 Human Breast Cancer Cells [J].
Oo, Phyu Synn ;
Yamaguchi, Yuya ;
Sawaguchi, Akira ;
Kyaw, Myat Tin Htwe ;
Choijookhuu, Narantsog ;
Ali, Mohmand Noor ;
Srisowanna, Naparee ;
Hino, Shin-ichiro ;
Hishikawa, Yoshitaka .
ACTA HISTOCHEMICA ET CYTOCHEMICA, 2018, 51 (01) :21-31