Mitochondrial respiratory control is lost during growth factor deprivation.
The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio confers a tight balance between cellular events that consume ATP and the rate of ATP production. However, after growth factor withdrawal, the cellular ATP/ADP ratio declines. To investigate these changes, mitochondria from growth factor-deprived cells isolated before the onset of apoptosis were characterized in vitro. Mitochondria from growth factor-deprived cells have lost their ability to undergo matrix condensation in response to ADP, which is accompanied by a failure to perform ADP-coupled respiration. At the time of analysis, mitochondria from growth factor-deprived cells were not depleted of cytochrome c and cytochrome c-dependent respiration was unaffected, demonstrating that the inhibition of the respiratory rate is not due to loss of cytochrome c. Agents that disrupt the mitochondrial outer membrane, such as digitonin, or maintain outer membrane exchange of adenine nucleotide, such as Bcl-x(L), restored ADP-dependent control of mitochondrial respiration. Together, these data suggest that the regulation of mitochondrial outer membrane permeability contributes to respiratory control.
Gottlieb
Eyal
E
Abramson Family Cancer Research Institute, and Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Armour
Sean M
SM
Thompson
Craig B
CB
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D006133:Growth Substances / Q000502:physiology*; D007377:Interleukin-3 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D016895:Culture Media, Serum-Free; D003574:Cytochrome c Group; D006133:Growth Substances; D007377:Interleukin-3; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D010100:Oxygen