Mitochondrial Dysfunction in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by recessive mutations in the SMN1 gene, globally affecting ~8-14 newborns per 100,000. The severity of the disease depends on the residual levels of functional survival of motor neuron protein, SMN. SMN is a ubiquitously expressed RNA binding protein involved in a plethora of cellular processes. In this review, we discuss the effects of SMN loss on mitochondrial functions in the neuronal and muscular systems that are the most affected in patients with spinal muscular atrophy. Our aim is to highlight how mitochondrial defects may contribute to disease progression and how restoring mitochondrial functionality may be a promising approach to develop new therapies. We also collected from previous studies a list of transcripts encoding mitochondrial proteins affected in various SMA models. Moreover, we speculate that in adulthood, when motor neurons require only very low SMN levels, the natural deterioration of mitochondria associated with aging may be a crucial triggering factor for adult spinal muscular atrophy, and this requires particular attention for therapeutic strategies.