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PGC-1a mediated mitochondrial biogenesis promotes recovery and survival of neuronal cells from cellular degeneration.
You, Wenting; Knoops, Kèvin; Berendschot, Tos T J M; Benedikter, Birke J; Webers, Carroll A B; Reutelingsperger, Chris P M; Gorgels, Theo G M F.
Afiliación
  • You W; University Eye Clinic Maastricht UMC+, Maastricht University Medical Center+, Maastricht, The Netherlands.
  • Knoops K; Department of Biochemistry, CARIM School for Cardiovascular Disease, Maastricht University, Maastricht, The Netherlands.
  • Berendschot TTJM; Department of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
  • Benedikter BJ; The Microscopy CORE lab, Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, The Netherlands.
  • Webers CAB; University Eye Clinic Maastricht UMC+, Maastricht University Medical Center+, Maastricht, The Netherlands.
  • Reutelingsperger CPM; University Eye Clinic Maastricht UMC+, Maastricht University Medical Center+, Maastricht, The Netherlands.
  • Gorgels TGMF; University Eye Clinic Maastricht UMC+, Maastricht University Medical Center+, Maastricht, The Netherlands.
Cell Death Discov ; 10(1): 180, 2024 Apr 17.
Article en En | MEDLINE | ID: mdl-38632223
ABSTRACT
Neurodegenerative disorders are characterized by the progressive loss of structure and function of neurons, often including the death of the neuron. Previously, we reported that, by removing the cell death stimulus, dying/injured neurons could survive and recover from the process of regulated cell death, even if the cells already displayed various signs of cellular damage. Now we investigated the role of mitochondrial dynamics (fission/fusion, biogenesis, mitophagy) in both degeneration and in recovery of neuronal cells. In neuronal PC12 cells, exposure to ethanol (EtOH) induced massive neurite loss along with widespread mitochondrial fragmentation, mitochondrial membrane potential loss, reduced ATP production, and decreased total mitochondrial volume. By removing EtOH timely all these mitochondrial parameters recovered to normal levels. Meanwhile, cells regrew neurites and survived. Study of the mitochondrial dynamics showed that autophagy was activated only during the cellular degeneration phase (EtOH treatment) but not in the recovery phase (EtOH removed), and it was not dependent on the Parkin/PINK1 mediated mitophagy pathway. Protein expression of key regulators of mitochondrial fission, phospho-Drp1Ser616 and S-OPA1, increased during EtOH treatment and recovered to normal levels after removing EtOH. In addition, the critical role of PGC-1α mediated mitochondrial biogenesis in cellular recovery was revealed inhibition of PGC-1α using SR-18292 after EtOH removal significantly impeded recovery of mitochondrial damage, regeneration of neurites, and cell survival in a concentration-dependent manner. Taken together, our study showed reversibility of mitochondrial morphological and functional damage in stressed neuronal cells and revealed that PGC-1α mediated mitochondrial biogenesis played a critical role in the cellular recovery. This molecular mechanism could be a target for neuroprotection and neurorescue in neurodegenerative diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Death Discov Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Death Discov Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos