A team at Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago discovers a role for mitochondria in SMA. They identified functional and structural defects to the cells’ power houses, called mitochondria, which contribute to the motor neuron’s degeneration. These defects occur before the onset of SMA symptoms.
Although the genetic cause of SMA has been identified, mechanisms underlying the vulnerability of other tissues are not well understood.
To study these mechanisms, the team carried out an in-depth analysis of gene expression in SMA mouse model, in which they unexpectedly found changes in many genes associated with mitochondria, the power houses of cells. Importantly, they found defects in the function of mitochondria in motor neurons from SMA mice. Furthermore, they found increased oxidative stress level and impaired mitochondrial membrane potential in motor neurons affected by SMA. Mitochondrial mobility was also impaired in SMA disease conditions and breaks in the mitochondrial network in primary motor neurons from SMA mice were also found, but with no change in mitochondria density. Intriguingly, these functional and structural deficiencies in the SMA mouse model occur during the pre-symptomatic stage of disease, suggesting a role in initiating SMA. Altogether, these findings reveal a critical role for mitochondrial defects in SMA pathogenesis and suggest a novel target for improving tissue health in the disease.
N. Miller, H. Shi, A. S. Zelikovich and Y-C Ma. Motor Neuron Mitochondrial Dysfunction in Spinal Muscular Atrophy. Hum Mol Genet. 2016 Aug 3.