Artículo de revista
IP3 receptor blockade restores autophagy and mitochondrial function in skeletal muscle fibers of dystrophic mice
Fecha
2018Registro en:
Biochimica et Biophysica Acta - Molecular Basis of Disease, Volumen 1864, Issue 11, 2018, Pages 3685-3695
1879260X
09254439
10.1016/j.bbadis.2018.08.042
Autor
Valladares, Denisse
Utreras Mendoza, Yildy
Campos, Cristian
Morales, Camilo
Díaz Vegas, Alexis
Contreras Ferrat, Ariel Eduardo
Westermeier, Francisco
Jaimovich Pérez, Enrique
Marchi, Saverio
Pinton, Paolo
Lavandero González, Sergio
Institución
Resumen
© 2018 Duchenne muscular dystrophy (DMD) is characterized by a severe and progressive destruction of muscle fibers associated with altered Ca2+ homeostasis. We have previously shown that the IP3 receptor (IP3R) plays a role in elevating basal cytoplasmic Ca2+ and that pharmacological blockade of IP3R restores muscle function. Moreover, we have shown that the IP3R pathway negatively regulates autophagy by controlling mitochondrial Ca2+ levels. Nevertheless, it remains unclear whether IP3R is involved in abnormal mitochondrial Ca2+ levels, mitochondrial dynamics, or autophagy and mitophagy observed in adult DMD skeletal muscle. Here, we show that the elevated basal autophagy and autophagic flux levels were normalized when IP3R was downregulated in mdx fibers. Pharmacological blockade of IP3R in mdx fibers restored both increased mitochondrial Ca2+ levels and mitochondrial membrane potential under resting conditions. Interestingly, mdx mitochondria changed from a fission to an elongated s