Related Experiment Video
Updated: May 31, 2026
A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
Inhibiting the Hif-1α-Drp1 axis alleviates mitochondrial dysfunction and reduces senescence-like changes in
Peng Yang1, Yiheng Yang2,3, Xiao Huang1
1Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, China.
Background:
Cellular senescence is a significant pathological process in acute myocardial infarction (AMI), yet its upstream regulatory mechanisms remain unclear. This study reveals that the HIF-1α /Drp1 signaling axis serves as a critical link between hypoxia and senescence-like changes in myocardial tissue by disrupting mitochondrial homeostasis.
Methods:
Using rat AMI model (in vivo) and hypoxia‑exposed H9c2 cardiomyocytes (in vitro), we assessed mitochondrial morphology, mtROS, and senescence markers. Genetic gain‑ and loss‑of‑function approaches were applied to modulate Drp1 and HIF‑1α. We further evaluated the effects of the mitochondrial fission inhibitor Mdivi‑1 and the SASP inhibitor Ruxolitinib on mitochondrial function, senescence, and apoptosis.
Results:
AMI/hypoxia activated the ERK1/2-Akt pathway, promoting Drp1 Ser616 phosphorylation and mitochondrial translocation, leading to excessive fission, mtROS burst, and senescence-like changes in myocardial tissue (in vivo) / cardiomyocyte senescence (in H9c2 cells). HIF-1α transcriptionally regulated Drp1 expression. Mdivi-1 restored mitochondrial dynamics, reduced SASP-related inflammation, and improved cardiac function, indicating a myocardial protective effect. Ruxolitinib suppressed Drp1 Ser616 phosphorylation and alleviated senescence, apoptosis, and pyroptosis.
Conclusion:
HIF-1α-mediated upregulation of Drp1 and ERK-dependent phosphorylation of Drp1 collectively drive mitochondrial dysfunction and senescence-like changes in myocardial tissue in AMI. Targeting these pathways or the SASP pathway represents a promising therapeutic strategy.
