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Hypoxia‐induced BNIP3 expression and mitophagy: in vivo comparison of the rat and the hypoxia‐tolerant mole rat, Spalax ehrenbergi
Author(s) -
Band Mark,
Joel Alma,
Hernandez Alvaro,
Avivi Aaron
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-122978
Subject(s) - biology , mitophagy , hypoxia (environmental) , microbiology and biotechnology , skeletal muscle , phenotype , reactive oxygen species , in vivo , autophagy , gene , endocrinology , oxygen , genetics , apoptosis , chemistry , organic chemistry
The blind subterranean mole rat of the Spalax ehrenbergi superspecies is an excellent animal model for hypoxic tolerance. Unique physiological, functional, and gene structure changes allow Spalax species to survive lower oxygen levels than most terrestrial animals. BNIP3 , an HIF‐1 dependent hypoxiaresponse gene, has a proapoptotic function;however, expression is suppressed in many types of cancers. Under hypoxic conditions, BNIP3 also functions as a mediator of mitochondrial autophagy, a survival adaptation to control ROS production and DNA damage. Using real‐time PCR and Western blotting, we investigated the impact of hypoxia on BNIP3 expression and mitophagy, in the skeletal muscle and heart, of the Rattus and two Spalax species. BNIP3 transcript, as well as protein levels, increased to significantly higher levels under hypoxia in Rattus tissues, with smaller changes in Spalax . Mitophagy was correlated with BNIP3 expression in the heart with an inverse correlation to hypoxia tolerance. A dense network of vessels in Spalax muscle may offer protection from physiological hypoxia, while the response in Rattus reflects the increase of hypoxic stress. In Spalax tissues, as in many cancers, BNIP3 expression and mitophagy are significantly less affected by hypoxia. Similar mechanisms, beneficial to organisms adapted to stressful environments, may also confer malignant cells with survival features. Understanding the molecular basis of such adaptations may enhance development of new therapeutic modalities.—Band, M., Joel, A., Hernandez, A., Avivi, A. Hypoxiainduced BNIP3 expression and mitophagy: in vivo comparison of the rat and the hypoxia‐tolerant mole rat, Spalax ehrenbergi . FASEB J. 23, 2327–2335 (2009)