Lipin-1 regulates Bnip3-mediated mitophagy in glycolytic muscle.

TitleLipin-1 regulates Bnip3-mediated mitophagy in glycolytic muscle.
Publication TypeJournal Article
Year of Publication2018
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Paginationfj201800374
Date Published2018 Jun 25
ISSN0892-6638
AbstractAutophagy of mitochondria (mitophagy) is essential for maintaining muscle mass and healthy skeletal muscle. Patients with heritable phosphatidic acid phosphatase lipin-1-null mutations present with severe rhabdomyolysis and muscle atrophy in glycolytic muscle fibers, which are accompanied with mitochondrial aggregates and reduced mitochondrial cytochrome c oxidase activity. However, the underlying mechanisms leading to muscle atrophy as a result of lipin-1 deficiency are still not clear. In this study, we found that lipin-1 deficiency in mice is associated with a marked accumulation of abnormal mitochondria and autophagic vacuoles in glycolytic muscle fibers. Our studies using lipin-1-deficient myoblasts suggest that lipin-1 participates in B-cell leukemia (BCL)-2 adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3)-regulated mitophagy by interacting with microtubule-associated protein 1A/1B-light chain (LC)3, which is an important step in the recruitment of mitochondria to nascent autophagosomes. The requirement of lipin-1 for Bnip3-mediated mitophagy was further verified in vivo in lipin-1-deficient green fluorescent protein-LC3 transgenic mice (lipin-1-GFP-LC3). Finally, we showed that lipin-1 deficiency in mice resulted in defective mitochondrial adaptation to starvation-induced metabolic stress and impaired contractile muscle force in glycolytic muscle fibers. In summary, our study suggests that deregulated mitophagy arising from lipin-1 deficiency is associated with impaired muscle function and may contribute to muscle rhabdomyolysis in humans.-Alshudukhi, A. A., Zhu, J., Huang, D., Jama, A., Smith, J. D., Wang, Q. J., Esser, K. A., Ren, H. Lipin-1 regulates Bnip3-mediated mitophagy in glycolytic muscle.
URLhttp://www.fasebj.org/doi/full/10.1096/fj.201800374?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
DOI10.1096/fj.201800374
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/29939786?dopt=Abstract
Short TitleFASEB J