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Defects in multiple complexes of the respiratory chain are present in ageing human colonic crypts

Lookup NU author(s): Dr Laura Greaves, Dr Martin Barron, Dr Stefan Plusa, Emeritus Professor Thomas Kirkwood, Professor John Mathers, Professor Robert Taylor, Professor Doug Turnbull

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Abstract

Mitochondrial DNA (mtDNA) mutations accumulate in a number of ageing tissues and are proposed to play a role in the ageing process. We have previously shown that colonic crypt stem cells accumulate somatic mtDNA point mutations during ageing. These mtDNA mutations result in the loss of the activity of complex IV (cytochrome c oxidase (COX)) of the respiratory chain in the stem cells and their progeny, producing colonic crypts which are entirely COX deficient. However it is not known whether the other complexes of the respiratory chain are similarly affected during ageing. Here we have used antibodies to individual subunits of complexes I-IV to investigate their expression in the colonic epithelium from human subjects aged 18-84. We show that in ∼50% of crypts with any form of respiratory chain deficiency, decreased expression of subunits of multiple complexes is observed. Furthermore we have sequenced the entire mitochondrial genome of a number of cells with multiple complex defects and have found a wide variety of point mutations in these cells affecting a number of different protein encoding and RNA encoding genes. Finally we discuss the possible mechanisms by which multiple respiratory chain complex defects may occur in these cells. © 2010 Elsevier Inc.


Publication metadata

Author(s): Greaves L, Barron M, Plusa S, Kirkwood T, Mathers J, Taylor R, Turnbull D

Publication type: Article

Publication status: Published

Journal: Experimental Gerontology

Year: 2010

Volume: 45

Issue: 7-8

Pages: 573-579

Print publication date: 22/01/2010

ISSN (print): 0531-5565

ISSN (electronic): 1873-6815

Publisher: Elsevier Inc

URL: http://dx.doi.org/10.1016/j.exger.2010.01.013

DOI: 10.1016/j.exger.2010.01.013

PubMed id: 20096767


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