Mitochondrial oxidative stress causes mitochondrial fragmentation

What is it about?

Mitochondria are dynamic organelles that undergo continual fusion and fission to maintain their morphology and functions, but the mechanism involved is still not clear. Here, we investigated the effect of mitochondrial oxidative stress triggered by high-fluence low-power laser irradiation (HFLPLI) on mitochondrial dynamics in human lung adenocarcinoma cells (ASTC-a-1) and African green monkey SV40-transformed kidney fibroblast cells (COS-7). Upon HF-LPLI-triggered oxidative stress, mitochondria displayed a fragmented structure, which was abolished by exposure to dehydroascorbic acid, a reactive oxygen species scavenger, indicating that oxidative stress can induce mitochondrial fragmentation. Further study revealed that HF-LPLI caused mitochondrial fragmentation by inhibiting fusion and enhancing fission. Mitochondrial translocation of the profission protein dynamin-related protein 1 (Drp1) was observed following HF-LPLI, demonstrating apoptosis-related activation of Drp1. Notably, overexpression of Drp1 increased mitochondrial fragmentation and promoted HF-LPLIinduced apoptosis through promoting cytochrome c release and caspase-9 activation, whereas overexpression of mitofusin 2 (Mfn2), a profusion protein, caused the opposite effects. Also, neither Drp1 overexpression nor Mfn2 overexpression affected mitochondrial reactive oxygen species generation, mitochondrial depolarization, or Bax activation. We conclude that mitochondrial oxidative stress mediated through Drp1 and Mfn2 causes an imbalance in mitochondrial fission–fusion, resulting in mitochondrial fragmentation, which contributes to mitochondrial and cell dysfunction.

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Why is it important?

Previous studies have demonstrated that high-fluence low-power laser irradiation (HF-LPLI) can induce mitochondrial oxidative stress in human lung adenocarcinoma cells (ASTC-a-1) and SV40-transformed African green monkey kidney fibroblast cells (COS-7) cells through selectively exciting the endogenous photoacceptor (cytochrome c oxidase) by laser irradiation (632.8 nm). The oxidative stress causes mitochondrial permeability transition pores to open for a long time, causes mitochondrial depolarization, cytochrome c release, and caspase-3 activation, and finally results in cell apoptosis. However, whether HF-LPLI-induced mitochondrial oxidative stress can induce mitochondrial morphological changes is still not clear. Thus, in the present study, we investigated the regulatory pathways involved in mitochondrial dynamics following HF-LPLI, using fluorescent imaging, western blot and flow cytometry techniques in ASTC-a-1 cells and COS-7 cells.