Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells

Congenital muscular dystrophy type 1A (MDC1A) is a severe muscle disorder caused by mutations in the laminin α2 gene. Here, the authors have investigated the bioenergetic profile in myogenic cells from MDC1A and LS patients. To confirm that the metabolic alterations were due to deficiency of laminin-211 in MDC1A cells, MDC1A myotubes were cultured in plates coated with recombinant laminin-211. Indeed, basal respiration, maximum respiration, and ATP production, as well as basal mitochondrial respiration and maximal mitochondrial respiration capacity, were normalized to control levels in the presence of laminin-211. The results indicate that absence of laminin α2 chain leads to downregulated PGC1α expression, which impairs mitochondrial biogenesis, causing a reduction of mitochondrial content that finally leads to a bioenergetic inefficiency in myoblasts and myotubes from MDC1A patients. The authors found dysregulated expression of genes related to energy production, apoptosis, and proteasome in myoblasts and myotubes. The data, for the first time, demonstrated an impairment of the bioenergetic status in human MDC1A and LS muscle cells, which could contribute to cell cycle disturbance and increased apoptosis.