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Ramos 2020 PLoS One

From Bioblast
Publications in the MiPMap
Ramos SV, Hughes MC, Delfinis LJ, Bellissimo CA, Perry CGR (2020) Mitochondrial bioenergetic dysfunction in the D2.mdx model of Duchenne muscular dystrophy is associated with microtubule disorganization in skeletal muscle. https://doi.org/10.1371/journal.pone.0237138

» PLoS One 15:e0237138. PMID: 33002037 Open Access

Ramos Sofhia V, Hughes Meghan C, Delfinis Luca J,  Bellissimo Catherine A,  Perry Christopher GR (2020) PLoS One

Abstract: In Duchenne muscular dystrophy, a lack of dystrophin leads to extensive muscle weakness and atrophy that is linked to cellular metabolic dysfunction and oxidative stress. This dystrophinopathy results in a loss of tethering between microtubules and the sarcolemma. Microtubules are also believed to regulate mitochondrial bioenergetics potentially by binding the outer mitochondrial membrane voltage dependent anion channel (VDAC) and influencing permeability to ADP/ATP cycling. The objective of this investigation was to determine if a lack of dystrophin causes microtubule disorganization concurrent with mitochondrial dysfunction in skeletal muscle, and whether this relationship is linked to altered binding of tubulin to VDAC. In extensor digitorum longus (EDL) muscle from 4-week old D2.mdx mice, microtubule disorganization was observed when probing for α-tubulin. This cytoskeletal disorder was associated with a reduced ability of ADP to stimulate respiration and attenuate H2O2 emission relative to wildtype controls. However, this was not associated with altered α-tubulin-VDAC2 interactions. These findings reveal that microtubule disorganization in dystrophin-deficient EDL is associated with impaired ADP control of mitochondrial bioenergetics, and suggests that mechanisms alternative to α-tubulin's regulation of VDAC2 should be examined to understand how cytoskeletal disruption in the absence of dystrophin may cause metabolic dysfunctions in skeletal muscle.

Bioblast editor: Plangger M O2k-Network Lab: CA Toronto Perry CG


Labels: MiParea: Respiration  Pathology: Myopathy 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS  Pathway: N, NS  HRR: Oxygraph-2k 

2023-01