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A Faster, High Resolution, mtPA-GFP-based Mitochondrial Fusion Assay Acquiring Kinetic Data of Multiple Cells in Parallel Using Confocal Microscopy
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A Faster, High Resolution, mtPA-GFP-based Mitochondrial Fusion Assay Acquiring Kinetic Data of Multiple Cells in Parallel Using Confocal Microscopy

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Pb induced mitochondrial fission of fibroblast cells via ATM activation

Yongmei Qi1, Lin Ma1, Sajid Naeem1

  • 1Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.

Journal of Hazardous Materials
|September 8, 2021
PubMed

Insights

Lead exposure disrupts mitochondrial shape by increasing fission and decreasing fusion. Cytoplasmic ATM acts as a key regulator in this lead-induced mitochondrial fragmentation process.

Area of Science:

  • Cell Biology
  • Toxicology
  • Mitochondrial Dynamics

Background:

  • Lead (Pb) exposure is known to induce mitophagy, a process of clearing damaged mitochondria.
  • The precise mechanisms by which lead affects mitochondrial fusion and fission, crucial upstream events of mitophagy, remain largely unknown.
  • The role of ATM (Ataxia-telangiectasia mutated) in lead's impact on mitochondrial dynamics requires further elucidation.

Purpose of the Study:

  • To investigate the effects of lead on mitochondrial fusion and fission processes.
  • To explore the involvement of ATM in lead-induced alterations of mitochondrial morphology.
  • To determine how ATM signaling connects to the regulation of mitochondrial dynamics under lead exposure.

Main Methods:

  • Analysis of mitochondrial network morphology using imaging techniques.
  • Western blotting and co-immunoprecipitation to assess the expression and interaction of key mitochondrial fusion and fission proteins (Drp1, Mfn2, Opa1).
  • Immunofluorescence microscopy to examine the localization of phosphorylated ATM (p-ATM) and its co-localization with mitochondrial proteins.
  • siRNA-mediated silencing of ATM to evaluate its role in lead-induced mitochondrial fragmentation.

Main Results:

  • Lead exposure significantly disrupted mitochondrial morphology, characterized by increased mitochondrial shortening and reduced mitochondrial footprints.
  • Lead elevated the expression and mitochondrial association of the fission protein Drp1, while suppressing the fusion proteins Mfn2 and Opa1.
  • Phosphorylation and mitochondrial translocation of Drp1 were markedly increased, alongside the detection of cytoplasmic ATM around mitochondria.
  • p-ATM co-localized more with Drp1 and p-Drp1 but less with Mfn2 and Opa1, and ATM silencing exacerbated lead-induced mitochondrial fission.

Conclusions:

  • Cytoplasmic ATM plays a critical role in regulating mitochondrial fission in response to lead exposure.
  • Lead-induced mitochondrial fragmentation is mediated through the modulation of fission and fusion protein dynamics, with ATM as a key signaling node.
  • These findings provide new insights into the molecular mechanisms underlying lead toxicity at the mitochondrial level.
Keywords:
ATMLead (Pb)Mitochondrial fissionMitochondrial fusion

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