Mislocalization of mitochondria and compromised renal function and oxidative stress resistance in Drosophila SesB mutants.
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.
Terhzaz
Selim
S
Integrative and Systems Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Cabrero
Pablo
P
Chintapalli
Venkateswara R
VR
Davies
Shireen-A
SA
Dow
Julian A T
JA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000473:pathology / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
D029721:Drosophila Proteins; D012333:RNA, Messenger; C491544:sesB protein, Drosophila; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D006861:Hydrogen Peroxide; D002118:Calcium