Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration

Pollard, Amelia; Shephard, Freya; Freed, James; Liddell, Susan; Chakrabarti, Lisa

Abstract

Carbonic anhydrase inhibitors are used to treat glaucoma and cancers. Carbonic anhydrases perform a crucial role in the conversion of carbon dioxide and water into bicarbonate and protons. However, there is little information about carbonic anhydrase isoforms during the process of ageing. Mitochondrial dysfunction is implicit in ageing brain and muscle. We have interrogated isolated mitochondrial fractions from young adult and middle aged mouse brain and skeletal muscle. We find an increase of tissue specific carbonic anhydrases in mitochondria from middle-aged brain and skeletal muscle. Mitochondrial carbonic anhydrase II was measured in the Purkinje cell degeneration (pcd5J) mouse model. In pcd5J we find mitochondrial carbonic anhydrase II is also elevated in brain from young adults undergoing a process of neurodegeneration. We show C.elegans exposed to carbonic anhydrase II have a dose related shorter lifespan suggesting that high CAII levels are in themselves life limiting. We show for the first time that the mitochondrial content of brain and skeletal tissue are exposed to significantly higher levels of active carbonic anhydrases as early as in middle-age. Carbonic anhydrases associated with mitochondria could be targeted to specifically modulate age related impairments and disease.

Citation

Pollard, A., Shephard, F., Freed, J., Liddell, S., & Chakrabarti, L. (2016). Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration. Aging, 8(10), 2425-2436. https://doi.org/10.18632/aging.101064

• Journal Article Type: Article
• Acceptance Date: Sep 25, 2016
• Online Publication Date: Oct 10, 2016
• Publication Date: Oct 10, 2016
• Deposit Date: Oct 25, 2016
• Publicly Available Date: Oct 25, 2016
• Journal: Aging
• Electronic ISSN: 1945-4589
• Publisher: Impact Journals
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 10
• Pages: 2425-2436
• DOI: https://doi.org/10.18632/aging.101064
• Keywords: mitochondria; ageing; skeletal muscle; brain; proteomics; carbonic anhydrase
• Public URL: https://nottingham-repository.worktribe.com/output/824139
• Publisher URL: http://www.aging-us.com/article/101064
• Contract Date: Oct 25, 2016