Cytosolic dynamin-related protein 1 (Drp1, also known as DNM1L) is required for both mitochondrial and peroxisomal fission. Drp1-dependent division of these organelles is facilitated by a number of adaptor proteins at mitochondrial and peroxisomal surfaces. To investigate the interplay of these adaptor proteins, we used gene-editing technology to create a suite of cell lines lacking the adaptors MiD49 (also known as MIEF2), MiD51 (also known as MIEF1), Mff and Fis1. Increased mitochondrial connectivity was observed following loss of individual adaptors, and this was further enhanced following the combined loss of MiD51 and Mff. Moreover, loss of adaptors also conferred increased resistance of cells to intrinsic apoptotic stimuli, with MiD49 and MiD51 showing the more prominent role. Using a proximity-based biotin labeling approach, we found close associations between MiD51, Mff and Drp1, but not Fis1. Furthermore, we found that MiD51 can suppress Mff-dependent enhancement of Drp1 GTPase activity. Our data indicates that Mff and MiD51 regulate Drp1 in specific ways to promote mitochondrial fission.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919635 | PMC |
| http://dx.doi.org/10.1242/jcs.185165 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Fatty acyl-coenzyme A activates mitochondrial division through oligomerization of MiD49 and MiD51.
Nat Cell Biol
May 2024
Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth College, Hanover, NH, USA.
Mitochondrial fission occurs in many cellular processes, but the regulation of fission is poorly understood. We show that long-chain acyl-coenzyme A (LCACA) activates two related mitochondrial fission proteins, MiD49 and MiD51, by inducing their oligomerization, which activates their ability to stimulate the DRP1 GTPase. The 1:1 stoichiometry of LCACA:MiD in the oligomer suggests interaction in the previously identified nucleotide-binding pocket, and a point mutation in this pocket reduces LCACA binding and LCACA-induced oligomerization for MiD51.
View Article and Find Full Text PDF[Role of mitochondrial dynamics in diabetic cardiomyopathy and regulatory mechanisms].
Sheng Li Xue Bao
February 2024
Department of Physiology and Pathophysiology, Air Force Medical University, Xi'an 710032, China.
Cardiovascular complications are the leading cause of death in diabetic patients. Among them, diabetic cardiomyopathy (DCM) is a type of specific cardiomyopathy excluding myocardial damage caused by hypertension and coronary heart disease. It is characterized by abnormal metabolism of cardiomyocytes and gradual decline of cardiac function.
View Article and Find Full Text PDFDynamin-Related Protein 1 Binding Partners MiD49 and MiD51 Increased Mitochondrial Fission In Vitro and Atherosclerosis in High-Fat-Diet-Fed ApoE Mice.
Int J Mol Sci
December 2023
Molecular Medical Laboratory, College of Basic Medical Science, Dalian Medical University, Dalian 116000, China.
Novel components of the mitochondrial fission machinery, mitochondrial dynamics proteins of 49 kDa (MiD49) and 51 kDa (MiD51), have been recently described, and their potential therapeutic targets for treating cardiovascular disease have been shown, including acute myocardial infarction (AMI), anthracycline cardiomyopathy and pulmonary arterial hypertension (PAH). Here, we examined the role of MiD49 and MiD51 in atherosclerosis. MiD49/51 expression was increased in the aortic valve endothelial cells (ECs) of high-fat diet-induced atherosclerosis in ApoEmice and IL-8-induced human umbilical vein endothelial cells (HUVECs), which accelerated dynamin-related protein 1 (Drp1)-mediated mitochondrial fission.
View Article and Find Full Text PDFThe Footprints of Mitochondrial Fission and Apoptosis in Fluoride-Induced Renal Dysfunction.
Biol Trace Elem Res
September 2024
Henan Key Laboratory of Environmental and Animal Product Safety, Henan University of Science and Technology, Kaiyuan Avenue 263, Luoyang, 471000, Henan, People's Republic of China.
Fluoride (F) is widely distributed in the environment and poses serious health risks to humans and animals. Although a good body of literature demonstrates a close relationship between F content and renal system performance, there is no satisfactory information on the involved intracellular routes. Hence, this study used histopathology and mitochondrial fission to explore fluorine-induced nephrotoxicity further.
View Article and Find Full Text PDFThe mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.
Cell Cycle
November 2023
Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Recent study had deepened our knowledge of the mitochondrial dynamics to classify mitochondrial fission into two types. To further clarify the relationship between the two distinct fission machinery and the four major adaptors of Drp1, we propose a model of mechanism elucidating the multiple functions of phospho-Drp1 with its adaptors during cell cycle and providing in-depth insights into the molecular basis and evolutionary implications in depth. The model highlights not only the clustering characteristics of different phospho-Drp1 with respective subsets of mitochondrial pro-fission adaptors but also the correlation, crosstalk and shifting between different clustering of phosphorylated Drp1-adaptors during different key fission situations.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!