title: The Drosophila effector caspase Dcp-1 regulates mitochondrial dynamics and autophagic flux via SesB.
abstract: Increasing evidence reveals that a subset of proteins participates in both the autophagy and apoptosis pathways, and this intersection is important in normal physiological contexts and in pathological settings. In this paper, we show that the Drosophila effector caspase, Drosophila caspase 1 (Dcp-1), localizes within mitochondria and regulates mitochondrial morphology and autophagic flux. Loss of Dcp-1 led to mitochondrial elongation, increased levels of the mitochondrial adenine nucleotide translocase stress-sensitive B (SesB), increased adenosine triphosphate (ATP), and a reduction in autophagic flux. Moreover, we find that SesB suppresses autophagic flux during midoogenesis, identifying a novel negative regulator of autophagy. Reduced SesB activity or depletion of ATP by oligomycin A could rescue the autophagic defect in Dcp-1 loss-of-function flies, demonstrating that Dcp-1 promotes autophagy by negatively regulating SesB and ATP levels. Furthermore, we find that pro-Dcp-1 interacts with SesB in a nonproteolytic manner to regulate its stability. These data reveal a new mitochondrial-associated molecular link between nonapoptotic caspase function and autophagy regulation in vivo.
authors.affiliation: The Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: Lindsay
authors.initials: L
authors.lastname: DeVorkin
authors.affiliation: The Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Nancy Erro
authors.initials: NE
authors.lastname: Go
authors.affiliation: The Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Ying-Chen Claire
authors.initials: YC
authors.lastname: Hou
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Moradian
authors.affiliation: The Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Morin
authors.affiliation: The Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada sgorski@bcgsc.ca.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Gorski
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D053470:Caspases, Effector / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008928:Mitochondria / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D009866:Oogenesis / Q000502:physiology; D010053:Ovary / Q000166:cytology / Q000502:physiology; D013217:Starvation / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D009840:Oligomycins; C491544:sesB protein, Drosophila; C031004:oligomycin A; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D020169:Caspases; D053470:Caspases, Effector; C103568:Dcp-1 protein, Drosophila