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

Terhzaz, S. , Cabrero, P. , Chintapalli, V.R., Davies, S.A. and Dow, J.A.T. (2010) Mislocalization of mitochondria and compromised renal function and oxidative stress resistance in Drosophila SesB mutants. Physiological Genomics, 41(1), pp. 33-41. (doi: 10.1152/physiolgenomics.00147.2009) (PMID:20009008) (PMCID:PMC2841493)

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Publisher's URL: http://dx.doi.org/10.1152/physiolgenomics.00147.2009


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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Chintapalli, Dr Venkateswara and Cabrero, Mr Pablo and Dow, Professor Julian and Terhzaz, Dr Selim and Davies, Professor Shireen
Authors: Terhzaz, S., Cabrero, P., Chintapalli, V.R., Davies, S.A., and Dow, J.A.T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Physiological Genomics
ISSN (Online):1531-2267
Published Online:15 December 2009

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
415661Spatiotemporal filtering in calcium control of mitochondrial functionJulian DowBiotechnology and Biological Sciences Research Council (BBSRC)BB/D013852/1RI MOLECULAR CELL & SYSTEMS BIOLOGY