Difference between revisions of "Hepple 2012 Abstract Bioblast"
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Mitochondrial alterations are strongly implicated in aging, particularly that of post-mitotic tissues like skeletal muscle. To date the majority of studies have examined this issue using mechanically isolated mitochondria. Given the fragmentation of the native mitochondrial architecture induced by this approach, and the stress this imposes on the organelle (e.g., potentiating ROS emission and sensitivity to an apoptotic challenge [1]), it is important to consider whether mitochondrial isolation affects the assessment of alterations in mitochondrial function in aging skeletal muscle. To this end, we compared alterations in mitochondrial function (respiration, reactive oxygen species [ROS] emission, and function of the mitochondrial permeability transition pore [mPTP]) in aging skeletal muscle between isolated mitochondria and saponin-permeabilized myofibers, the latter representing a method that preserves mitochondrial architecture. Strikingly, we observed that routine mechanical isolation of mitochondria profoundly exaggerated the impact of aging on all indices of mitochondrial function, whereas permeabilized myofibers from aged muscles had no change in respiratory capacity, and relatively modest alterations in ROS emission and mPTP function [2]. In addition to having important implications for our understanding of the severity of mitochondrial dysfunction in aging skeletal muscle, our results also suggest that vulnerabilities in aging mitochondria from skeletal muscle may be at least partially compensated for by the mitochondrial network structure ''in vivo'' and these vulnerabilities become unmasked following organelle isolation. The implications of these findings for our understanding of aging on mitochondrial function will be discussed. | Mitochondrial alterations are strongly implicated in aging, particularly that of post-mitotic tissues like skeletal muscle. To date the majority of studies have examined this issue using mechanically isolated mitochondria. Given the fragmentation of the native mitochondrial architecture induced by this approach, and the stress this imposes on the organelle (e.g., potentiating ROS emission and sensitivity to an apoptotic challenge [1]), it is important to consider whether mitochondrial isolation affects the assessment of alterations in mitochondrial function in aging skeletal muscle. To this end, we compared alterations in mitochondrial function (respiration, reactive oxygen species [ROS] emission, and function of the mitochondrial permeability transition pore [mPTP]) in aging skeletal muscle between isolated mitochondria and saponin-permeabilized myofibers, the latter representing a method that preserves mitochondrial architecture. Strikingly, we observed that routine mechanical isolation of mitochondria profoundly exaggerated the impact of aging on all indices of mitochondrial function, whereas permeabilized myofibers from aged muscles had no change in respiratory capacity, and relatively modest alterations in ROS emission and mPTP function [2]. In addition to having important implications for our understanding of the severity of mitochondrial dysfunction in aging skeletal muscle, our results also suggest that vulnerabilities in aging mitochondria from skeletal muscle may be at least partially compensated for by the mitochondrial network structure ''in vivo'' and these vulnerabilities become unmasked following organelle isolation. The implications of these findings for our understanding of aging on mitochondrial function will be discussed. | ||
# [http://www.ncbi.nlm.nih.gov/pubmed/21512578 Picard M, Taivassalo T, Ritchie D, Wright KJ, Thomas MM, Romestaing C, Hepple RT (2011) Mitochondrial structure and function are disrupted by standard isolation methods. PLoS One 6: e18317. Open Access] | |||
[2] [http://www.ncbi.nlm.nih.gov/pubmed/20849523 Picard M, Ritchie D, Wright KJ, Romestaing C, Thomas MM, Rowan SL, Taivassalo T, Hepple RT (2010) Mitochondrial functional impairment with aging is exaggerated in isolated mitochondria compared to permeabilized myofibers. Aging Cell 9: 1032-1046] | [2] [http://www.ncbi.nlm.nih.gov/pubmed/20849523 Picard M, Ritchie D, Wright KJ, Romestaing C, Thomas MM, Rowan SL, Taivassalo T, Hepple RT (2010) Mitochondrial functional impairment with aging is exaggerated in isolated mitochondria compared to permeabilized myofibers. Aging Cell 9: 1032-1046] | ||
|keywords=Aging, mPTP, | |keywords=Aging, mPTP, | ||
|mipnetlab=CA Montreal Hepple RT | |mipnetlab=CA Montreal Hepple RT | ||
|journal=Mitochondr Physiol Network | |journal=Mitochondr Physiol Network | ||
Revision as of 10:18, 28 November 2012
| Hepple RT, Picard M, Taivassalo T (2012) Is latent mitochondrial dysfunction in aging muscle exposed through mitochondrial isolation? Mitochondr Physiol Network 17.12. |
Link: MiPNet17.12 Bioblast 2012 - Open Access
Hepple RT, Picard M, Taivassalo T (2012)
Event: Bioblast 2012
Mitochondrial alterations are strongly implicated in aging, particularly that of post-mitotic tissues like skeletal muscle. To date the majority of studies have examined this issue using mechanically isolated mitochondria. Given the fragmentation of the native mitochondrial architecture induced by this approach, and the stress this imposes on the organelle (e.g., potentiating ROS emission and sensitivity to an apoptotic challenge [1]), it is important to consider whether mitochondrial isolation affects the assessment of alterations in mitochondrial function in aging skeletal muscle. To this end, we compared alterations in mitochondrial function (respiration, reactive oxygen species [ROS] emission, and function of the mitochondrial permeability transition pore [mPTP]) in aging skeletal muscle between isolated mitochondria and saponin-permeabilized myofibers, the latter representing a method that preserves mitochondrial architecture. Strikingly, we observed that routine mechanical isolation of mitochondria profoundly exaggerated the impact of aging on all indices of mitochondrial function, whereas permeabilized myofibers from aged muscles had no change in respiratory capacity, and relatively modest alterations in ROS emission and mPTP function [2]. In addition to having important implications for our understanding of the severity of mitochondrial dysfunction in aging skeletal muscle, our results also suggest that vulnerabilities in aging mitochondria from skeletal muscle may be at least partially compensated for by the mitochondrial network structure in vivo and these vulnerabilities become unmasked following organelle isolation. The implications of these findings for our understanding of aging on mitochondrial function will be discussed.
• Keywords: Aging, mPTP
• O2k-Network Lab: CA Montreal Hepple RT
Labels:
Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Aging; Senescence"Aging; Senescence" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.
Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue, Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.
HRR: Oxygraph-2k
Affiliations and author contributions
Russell T Hepple (1,2), Martin Picard (2), Tanja Taivassalo (2)
(1) McGill University Health Centre; Email: [email protected]
(2) Department of Kinesiology, McGill University, Montreal, QC, CANADA
