BNIP3 plays a role in the atrophy of muscle fibers in patients with late-onset Pompe disease (LOPD), according to a new study presented at the 18th Annual WorldSymposium 2022. Their results “open the door to potential new treatments targeting BNIP3 to reduce its deleterious effects on muscle fiber atrophy in Pompe disease,” they said.

Pompe disease is characterized by progressive muscle weakness and atrophy. However, the mechanism of how the disease leads to muscle fiber atrophy is not well understood.

Here, a team of researchers from the UK, Spain, and Germany studied the potential role of different molecules that may play a role in the process of muscle atrophy in Pompe disease and identified BNIP3 as a potential mediator of muscular atrophy. When they analyzed the muscle fibers, the researchers found that vacuolated muscle fibers were smaller than nonvacuolated ones, which express BNIP3. 

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Through immunohistochemistry experiments, the researchers showed that the expression of BNIP3 was likely regulated by the inhibition of AKT-mTOR pathway. This, they said, leads to the phosphorylation of ULK1, a kinase that plays a role in autophagy.

Similarly, myotubes obtained from patients with LOPD were smaller and expressed BNIP3. When they transfected BNIP3 into control myotubes, the researchers found that the myotubes became severely atrophied.

“These findings suggest a cascade with inhibition of the AKT-mTOR pathway, activation of expression of BNIP3 leading to progressive muscle fiber atrophy,” the researchers concluded. BNIP3 is a member of the apoptotic Bcl-2 protein family, which acts as a pro-apoptotic factor by interacting with antiapoptotic proteins such as E1B and Bcl2.

These findings were presented virtually on February 7, 2022, by Jordi Diaz-Manera, MD, PhD, Professor of Neuromuscular Diseases, and Consultant Neurologist at Newcastle University and Newcastle Hospitals National Health Service Foundation Trust in England.


Diaz-Manera J, Carrasco A, Fernández-Simon E, et al. BNIP3 is involved in muscle fiber atrophy in late-onset Pompe disease patients. Mol Genet Metab. 2022;135(2):S37-S38. doi:10.1016/j.ymgme.2021.11.083