Magri 2024 Cell Death Discov

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Publications in the MiPMap
Magrì A, Lipari CLR, Caccamo A, Battiato G, Conti Nibali S, De Pinto V, Guarino F, Messina A (2024) AAV-mediated upregulation of VDAC1 rescues the mitochondrial respiration and sirtuins expression in a SOD1 mouse model of inherited ALS. Cell Death Discov 10:178. https://doi.org/10.1038/s41420-024-01949-w

Β» PMID: 38627359 Open Access

Magri Andrea, Lipari Cristiana Lucia Rita, Caccamo Antonella, Battiato Giuseppe, Conti Nibali Stefano, De Pinto Vito, Guarino Francesca, Messina Angela (2024) Cell Death Discov

Abstract: Mitochondrial dysfunction represents one of the most common molecular hallmarks of both sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder caused by the selective degeneration and death of motor neurons. The accumulation of misfolded proteins on and within mitochondria, as observed for SOD1 G93A mutant, correlates with a drastic reduction of mitochondrial respiration and the inhibition of metabolites exchanges, including ADP/ATP and NAD+/NADH, across the Voltage-Dependent Anion-selective Channel 1 (VDAC1), the most abundant channel protein of the outer mitochondrial membrane. Here, we show that the AAV-mediated upregulation of VDAC1 in the spinal cord of transgenic mice expressing SOD1 G93A completely rescues the mitochondrial respiratory profile. This correlates with the increased activity and levels of key regulators of mitochondrial functions and maintenance, namely the respiratory chain Complex I and the sirtuins (Sirt), especially Sirt3. Furthermore, the selective increase of these mitochondrial proteins is associated with an increase in Tom20 levels, the receptor subunit of the TOM complex. Overall, our results indicate that the overexpression of VDAC1 has beneficial effects on ALS-affected tissue by stabilizing the Complex I-Sirt3 axis.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: IT Catania Messina A


Labels: MiParea: Respiration  Pathology: Neurodegenerative 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Homogenate 


Coupling state: ET, LEAK, OXPHOS  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2024-07 

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