Zhao 2022 J Cell Sci

From Bioblast
Publications in the MiPMap
Zhao Q, Yan S, Lu J, Parker DJ, Wu H, Sun Q, Crossman DK, Liu S, Wang Q, Sesaki H, Mitra K, Liu K, Jiao K (2022) Drp1 regulates transcription of ribosomal protein genes in embryonic hearts. https://doi.org/10.1242/jcs.258956

Β» J Cell Sci 135:jcs258956. PMID: 35099001 Open Access

Zhao Qiancong,  Yan Shun,  Lu Jin,  Parker Danitra J,  Wu Huiying,  Sun Qianchuang,  Crossman David K,  Liu Shanrun,  Wang Qin,  Sesaki Hiromi,  Mitra Kasturi,  Liu Kexiang,  Jiao Kai (2022) J Cell Sci

Abstract: Mitochondrial dysfunction causes severe congenital cardiac abnormalities and prenatal/neonatal lethality. The lack of sufficient knowledge regarding how mitochondrial abnormalities affect cardiogenesis poses a major barrier for the development of clinical applications that target mitochondrial deficiency-induced inborn cardiomyopathies. Mitochondrial morphology, which is regulated by fission and fusion, plays a key role in determining mitochondrial activity. Dnm1l encodes a dynamin-related GTPase, Drp1, which is required for mitochondrial fission. To investigate the role of Drp1 in cardiogenesis during the embryonic metabolic shift period, we specifically inactivated Dnm1l in second heart field-derived structures. Mutant cardiomyocytes in the right ventricle (RV) displayed severe defects in mitochondrial morphology, ultrastructure and activity. These defects caused increased cell death, decreased cell survival, disorganized cardiomyocytes and embryonic lethality. By characterizing this model, we reveal an AMPK-SIRT7-GABPB axis that relays the reduced cellular energy level to decrease transcription of ribosomal protein genes in cardiomyocytes. We therefore provide the first genetic evidence in mouse that Drp1 is essential for RV development. Our research provides further mechanistic insight into how mitochondrial dysfunction causes pathological molecular and cellular alterations during cardiogenesis. β€’ Keywords: Drp1, Heart development, RP gene transcription β€’ Bioblast editor: Plangger M


Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression  Pathology: Cardiovascular, Myopathy  Stress:Mitochondrial disease  Organism: Mouse  Tissue;cell: Heart  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k 

2022-12 

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