ERK1/2-dependent TSPO overactivation associates with the loss of mitophagy and mitochondrial respiration in ALS.

ABSTRACT: Mitochondrial dysfunction and the loss of mitophagy, aimed at recycling irreversibly damaged organelles, contribute to the onset of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease affecting spinal cord motor neurons. In this work, we showed that the reduction of mitochondrial respiration, exactly oxygen flows linked to ATP production and maximal capacity, correlates with the appearance of the most common ALS motor symptoms in a transgenic mouse model expressing SOD1 G93A mutant. This is the result of the equal inhibition in the respiration linked to complex I and II of the electron transport chain, but not their protein levels. Since the overall mitochondrial mass was unvaried, we investigated the expression of the Translocator Protein (TSPO), a small mitochondrial p

SUBMITTER: Magri A 

PROVIDER: S-EPMC9931716 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature