hnRNP R regulates mitochondrial movement and membrane potential in axons of motoneurons

Neurobiol Dis. 2024 Feb 24:106454. doi: 10.1016/j.nbd.2024.106454. Online ahead of print.ABSTRACTAxonal mitochondria defects are early events in the pathogenesis of motoneuron disorders such as spinal muscular atrophy and amyotrophic lateral sclerosis. The RNA-binding protein hnRNP R interacts with different motoneuron disease-related proteins such as SMN and TDP-43 and has important roles in axons of motoneurons, including axonal mRNA transport. However, whether hnRNP R also modulates axonal mitochondria is currently unknown. Here, we show that axonal mitochondria exhibit altered function and motility in hnRNP R-deficient motoneurons. Motoneurons lacking hnRNP R show decreased anterograde and increased retrograde transport of mitochondria in axons. Furthermore, hnRNP R-deficiency leads to mitochondrial hyperpolarization, caused by decreased complex I and reversed complex V activity within the respiratory chain. Taken together, our data indicate a role for hnRNP R in regulating transport and maintaining functionality of axonal mitochondria in motoneurons.PMID:38408684 | DOI:10.1016/j.nbd.2024.106454
Source: Neurobiology of Disease - Category: Neurology Authors: Source Type: research