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Physiol. Genomics 41: 33-41, 2010. First published December 15, 2009; doi:10.1152/physiolgenomics.00147.2009
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Received 31 August 2009; accepted in final form 10 December 2009.
Physiological Genomics 41:33-41 (2010)
Copyright © 2010 the American Physiological Society © 2010 American Physiological Society

Research Articles

Mislocalization of mitochondria and compromised renal function and oxidative stress resistance in Drosophila SesB mutants

Selim Terhzaz 1, Pablo Cabrero 1, Venkateswara R. Chintapalli 1, Shireen-A. Davies 1 and Julian A. T. Dow 1,2

1Integrative and Systems Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom; and
2Department of Clinical Laboratory Sciences, College of Clinical and Applied Medical Sciences, Kind Saud University, Riyadh, Kingdom of Saudi Arabia

Mitochondria accumulate at sites of intense metabolic activity within cells, but the adaptive value of this placement is not clear. In Drosophila, sesB encodes the ubiquitous isoform of adenine nucleotide translocase (ANT, the mitochondrial inner membrane ATP/ADP exchanger); null alleles are lethal, whereas hypomorphic alleles display sensitivity to a range of stressors. In the adult renal tubule, which is densely packed with mitochondria and hence enriched for sesB, both hypomorphic alleles and RNA interference knockdowns cause the mitochondria to lose their highly polarized distribution in the tissue and to become rounded. Basal cytoplasmic and mitochondrial calcium levels are both increased, and neuropeptide calcium response compromised, with concomitant defects in fluid secretion. The remaining mitochondria in sesB mutants are overactive and maintain depleted cellular ATP levels while generating higher levels of hydrogen peroxide than normal. When sesB expression is knocked down in just tubule principal cells, the survival of the whole organism upon oxidative stress is reduced, implying a limiting role for the tubule in homeostatic response to stressors. The physiological impacts of defective ANT expression are thus widespread and diverse.

Drosophila melanogaster; Malpighian tubule; adenine nucleotide translocase; mitochondria







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