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

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

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Authors

Amelia Pollard

Freya Shephard

James Freed

Susan Liddell

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LISA CHAKRABARTI LISA.CHAKRABARTI@NOTTINGHAM.AC.UK
Professor of Mitochondrial Biology



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

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