Removal or masking of phosphatidylinositol(4,5)bisphosphate from the outer mitochondrial membrane causes mitochondrial fragmentation.
Mitochondria are central players in programmed cell death and autophagy. While phosphoinositides are well established regulators of membrane traffic, cellular signalling and the destiny of certain organelles, their presence and role for mitochondria remain elusive. In this study we show that removal of PtdIns(4,5)P₂ by phosphatases or masking the lipid with PH domains leads to fission of mitochondria and increased autophagy. Induction of general autophagy by amino acid starvation also coincides with the loss of mitochondrial PtdIns(4,5)P₂, suggesting an important role for this lipid in the processes that govern mitophagy. Our findings reveal that PKCα can rescue the removal or masking of PtdIns(4,5)P₂, indicating that the inositol lipid is upstream of PKC.
The Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, UK
Erika
E
Rosivatz
Rudiger
R
Woscholski
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D005934:Glucagon / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000502:physiology*; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000502:physiology; D014407:Tumor Cells, Cultured
D019269:Phosphatidylinositol 4,5-Diphosphate; D005934:Glucagon; D051571:Protein Kinase C-alpha