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A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
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Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH-

Chenyang Duan1, Lei Kuang1, Xinming Xiang1

  • 1State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Army Medical University, 400042, Chongqing, P. R. China.

Cell Death & Disease
|April 22, 2020
PubMed

Insights

Dynamin-related protein 1 (Drp1) plays a key role in ischemic injury by disrupting mitochondrial homeostasis. It inhibits mitophagy, promotes apoptosis, and exacerbates metabolic disorders, worsening overall mitochondrial function.

Area of Science:

  • Mitochondrial Biology
  • Cellular Stress Response
  • Ischemic Pathophysiology

Background:

  • Mitochondrial homeostasis is crucial for cellular survival, especially during ischemic injury.
  • The precise mechanisms by which mitochondria adapt or fail during ischemia remain incompletely understood.
  • Dynamin-related protein 1 (Drp1) is a key regulator of mitochondrial dynamics, but its role in ischemic injury is unclear.

Purpose of the Study:

  • To investigate the role of dynamin-related protein 1 (Drp1) in the adaptation of mitochondrial homeostasis to ischemic injury.
  • To elucidate the molecular mechanisms by which Drp1 influences mitochondrial morphology, mitophagy, apoptosis, and metabolic dysfunction during ischemia.

Main Methods:

  • Analysis of mitochondrial morphology and function in vascular tissues at different stages of ischemic injury.
  • Investigation of Drp1 expression and activation.
  • Assessment of mitophagy markers, including mito-Clec16a and mito-Parkin recruitment.
  • Evaluation of apoptosis pathways, including BAX translocation and Cytochrome C release.
  • Measurement of metabolic parameters and mitochondrial glutathione levels.

Main Results:

  • Ischemic injury altered mitochondrial morphology early and caused dysfunction later.
  • Drp1 inhibited mitophagy by upregulating mito-Clec16a, suppressing mito-Parkin recruitment and autophagosome formation.
  • Ischemia-induced Drp1 activation promoted apoptosis via BAX translocation and Cytochrome C release, activating caspase-3/-9.
  • Drp1 mediated metabolic disorders, reduced mitochondrial glutathione, increased reactive oxygen species (ROS), and worsened mitochondrial dysfunction.

Conclusions:

  • Drp1 plays a critical role in exacerbating mitochondrial dysfunction and cellular damage following ischemic injury.
  • Targeting Drp1 may offer a therapeutic strategy to mitigate the detrimental effects of ischemia on mitochondrial homeostasis.

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