Mitochondrial viability in mouse and human postmortem brain.
Neuronal function in the brain requires energy in the form of ATP, and mitochondria are canonically associated with ATP production in neurons. The electrochemical gradient, which underlies the mitochondrial transmembrane potential (DeltaPsi(mem)), is harnessed for ATP generation. Here we show that DeltaPsi(mem) and ATP-production can be engaged in mitochondria isolated from human brains up to 8.5 h postmortem. Also, a time course of postmortem intervals from 0 to 24 h using mitochondria isolated from mouse cortex reveals that DeltaPsi(mem) in mitochondria can be reconstituted beyond 10 h postmortem. It was found that complex I of the mitochondrial electron transport chain was affected adversely with increasing postmortem intervals. Mitochondria isolated from postmortem mouse brains maintain the ability to produce ATP, but rates of production decreased with longer postmortem intervals. Furthermore, we show that postmortem brain mitochondria retain their DeltaPsi(mem) and ATP-production capacities following cryopreservation. Our finding that DeltaPsi(mem) and ATP-generating capacity can be reinitiated in brain mitochondria hours after death indicates that human postmortem brains can be an abundant source of viable mitochondria to study metabolic processes in health and disease. It is also possible to archive these mitochondria for future studies.
Barksdale
Keri A
KA
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA.
Perez-Costas
Emma
E
Gandy
Johanna C
JC
Melendez-Ferro
Miguel
M
Roberts
Rosalinda C
RC
Bijur
Gautam N
GN
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D011180:Postmortem Changes; D013997:Time Factors
D000255:Adenosine Triphosphate
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