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Updated: Aug 6, 2026

Assessment of Mitochondrial Fission/Fusion Dynamics in Kidney Proximal Tubular Cells
Published on: November 14, 2025
Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons
Mark J Barsoum1, Hua Yuan, Akos A Gerencser
1Apoptosis and Cell Death Program, Burnham Institute for Medical Research, La Jolla, CA, USA.
Abstract:
Mitochondria are present as tubular organelles in neuronal projections. Here, we report that mitochondria undergo profound fission in response to nitric oxide (NO) in cortical neurons of primary cultures. Mitochondrial fission by NO occurs long before neurite injury and neuronal cell death. Furthermore, fission is accompanied by ultrastructural damage of mitochondria, autophagy, ATP decline and generation of free radicals. Fission is occasionally asymmetric and can be reversible. Strikingly, mitochondrial fission is also an early event in ischemic stroke in vivo. Mitofusin 1 (Mfn1) or dominant-negative Dynamin related protein 1 (Drp1(K38A)) inhibits mitochondrial fission induced by NO, rotenone and Amyloid-beta peptide. Conversely, overexpression of Drp1 or Fis1 elicits fission and increases neuronal loss. Importantly, NO-induced neuronal cell death was mitigated by Mfn1 and Drp1(K38A). Thus, persistent mitochondrial fission may play a causal role in NO-mediated neurotoxicity.
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