title: Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration.
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. Inpcd5Jwe find mitochondrial carbonic anhydrase II is also elevated in brain from young adults undergoing a process of neurodegeneration. We showC.elegansexposed 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.
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, LE12 5RD, UK.
authors.forename: Amelia
authors.initials: A
authors.lastname: Pollard
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, LE12 5RD, UK.
authors.forename: Freya
authors.initials: F
authors.lastname: Shephard
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, LE12 5RD, UK.
authors.forename: James
authors.initials: J
authors.lastname: Freed
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington, LE12 5RD, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Liddell
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington, LE12 5RD, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Chakrabarti
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D017173:Caenorhabditis elegans; D024402:Carbonic Anhydrase II / Q000378:metabolism*; D008136:Longevity / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism; D040901:Proteomics
chemical_list: D024402:Carbonic Anhydrase II
keywords: ageing; brain; carbonic anhydrase; mitochondria; proteomics; skeletal muscle