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

Physiol Genomics. 2010 Mar 3;41(1):33-41. doi: 10.1152/physiolgenomics.00147.2009. Epub 2009 Dec 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Biological Transport
  • Calcium / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism*
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Hydrogen Peroxide / metabolism
  • Kidney / pathology
  • Kidney / physiopathology*
  • Kidney Function Tests
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Mitochondria / metabolism*
  • Mitochondrial ADP, ATP Translocases / genetics*
  • Mitochondrial ADP, ATP Translocases / metabolism
  • Mutation / genetics*
  • Organ Specificity / genetics
  • Oxidative Stress*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Analysis

Substances

  • Drosophila Proteins
  • RNA, Messenger
  • sesB protein, Drosophila
  • Adenosine Triphosphate
  • Mitochondrial ADP, ATP Translocases
  • Hydrogen Peroxide
  • Calcium