Holloway 2018 Cell Rep

Holloway GP, Holwerda AM, Miotto PM, Dirks ML, Verdijk LB, van Loon LJC (2018) Age-associated impairments in mitochondrial ADP sensitivity contribute to redox stress in senescent human skeletal muscle. Cell Rep 22:2837–48.

» Open Access

Holloway GP, Holwerda AM, Miotto PM, Dirks ML, Verdijk LB, van Loon LJC (2018) Cell Rep

Abstract: It remains unknown if mitochondrial bioenergetics are altered with aging in humans. We established an in vitro method to simultaneously determine mitochondrial respiration and H₂O₂ emission in skeletal muscle tissue across a range of biologically relevant ADP concentrations. Using this approach, we provide evidence that, although the capacity for mitochondrial H₂O₂ emission is not increased with aging, mitochondrial ADP sensitivity is impaired. This resulted in an increase in mitochondrial H₂O₂ and the fraction of electron leak to H₂O₂, in the presence of virtually all ADP concentrations examined. Moreover, although prolonged resistance training in older individuals increased muscle mass, strength, and maximal mitochondrial respiration, exercise training did not alter H₂O₂ emission rates in the presence of ADP, the fraction of electron leak to H₂O₂, or the redox state of the muscle. These data establish that a reduction in mitochondrial ADP sensitivity increases mitochondrial H₂O₂ emission and contributes to age-associated redox stress. • Keywords: Amplex Red in muscle fibers, Buffer Z, Blebbistatin • Bioblast editor: Kandolf G • O2k-Network Lab: CA Guelph Holloway GP

Labels: MiParea: Respiration  Pathology: Aging;senescence  Stress:Oxidative stress;RONS  Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Regulation: ADP  Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k, O2k-Fluorometer 

2018-03, AmR