The two Drosophila cytochrome C proteins can function in both respiration and caspase activation

EMBO J. 2006 Jan 11;25(1):232-43. doi: 10.1038/sj.emboj.7600920. Epub 2005 Dec 15.


Cytochrome C has two apparently separable cellular functions: respiration and caspase activation during apoptosis. While a role of the mitochondria and cytochrome C in the assembly of the apoptosome and caspase activation has been established for mammalian cells, the existence of a comparable function for cytochrome C in invertebrates remains controversial. Drosophila possesses two cytochrome c genes, cyt-c-d and cyt-c-p. We show that only cyt-c-d is required for caspase activation in an apoptosis-like process during spermatid differentiation, whereas cyt-c-p is required for respiration in the soma. However, both cytochrome C proteins can function interchangeably in respiration and caspase activation, and the difference in their genetic requirements can be attributed to differential expression in the soma and testes. Furthermore, orthologues of the apoptosome components, Ark (Apaf-1) and Dronc (caspase-9), are also required for the proper removal of bulk cytoplasm during spermatogenesis. Finally, several mutants that block caspase activation during spermatogenesis were isolated in a genetic screen, including mutants with defects in spermatid mitochondrial organization. These observations establish a role for the mitochondria in caspase activation during spermatogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Carrier Proteins / genetics
  • Caspases / genetics
  • Caspases / metabolism*
  • Cell Respiration* / genetics
  • Cytochromes c / analysis
  • Cytochromes c / genetics
  • Cytochromes c / metabolism*
  • Drosophila / enzymology
  • Drosophila / physiology*
  • Drosophila Proteins / analysis
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Enzyme Activation
  • Genes, Lethal
  • Infertility, Male / enzymology
  • Infertility, Male / genetics
  • Male
  • Mitochondria / physiology
  • Molecular Sequence Data
  • Mutation
  • Spermatids / cytology
  • Spermatids / enzymology
  • Spermatogenesis* / genetics
  • Transcription Factors / genetics


  • Carrier Proteins
  • Drosophila Proteins
  • Transcription Factors
  • bicoid interacting protein 1, Drosophila
  • cytochrome c distal, Drosophila
  • cytochrome c proximal, Drosophila
  • dark protein, Drosophila
  • Cytochromes c
  • Caspases
  • dronc protein, Drosophila