Mitochondria, oxidative stress, and antioxidant defences.

Abstract

Mitochondria are strongly involved in production of reactive oxygen species, considered today as the main pathogenic agent of many diseases. A vicious circle of oxidative stress and damage to cellular structures can lead to either cell death by apoptosis or to a cellular energetic decline and ageing. The early involvement of mitochondria in apoptosis includes expression of pro-apoptotic factors, release of cytochrome c from the inter-membrane space and opening of the permeability transition pore: cytochrome c release appears to precede pore opening. The mitochondrial theory of ageing considers somatic mutations (deletions) of mitochondrial DNA induced by oxygen radicals as the primary cause of energy decline; experimentally, Complex I appears to be mostly affected. We have developed the Pasteur effect (enhancement of lactate production by mitochondrial inhibition) as a bio-marker of mitochondrial bioenergetics in human platelets, and found it to be decreased in aged individuals. Cells counteract oxidative stress by antioxidants; among lipophilic antioxidants coenzyme Q is the only one of endogenous biosynthesis; exogenous coenzyme Q, however, may protect cells from oxidative stress in vivo.

Periods without agitation diminish platelet mitochondrial function during storage

“…This cyclic superoxide production has been termed a "vicious circle." 16 In addition, prolonged hypoxia can induce PLTs to switch to anaerobic respiration with increased glucose utilization and lactate production, which leads to a decline of pH levels.…”

“…[13][14][15] Interruptions of agitation are also known to depolarize MMP in PLTs. 1 While mitochondria are a known source and target of oxidative stress, 16 less is known about how periods without agitation influence the generation of PLT reactive oxygen species (ROS) and the effects of ROS on PLT mitochondria.…”

Oxidative Stress Profiling:

“…For example, in the process of producing required energy in mitochondria (ATP), toxic ROS/RNS are also produced through the oxygen's being utilized. [4][5][6][7] All organisms represent a history of evolutionary trade-offs. These processes played an important central role in molding the many different and interacting processes making up all living organisms.…”

Increased transcription of mitochondrial genes for Complex I in human platelets during ageing

“…Complex I is the largest and the most unexplored one although it represents the key enzyme of the mitochondrial electron chain. Furthermore, since seven out of the 13 polypeptides encoded by mtDNA belong to Complex I (reduced nicotinamide adenine dinucleotide (NADH)-coenzyme Q reductase), it is expected that this enzyme should be mostly a¡ected by ageing [6]. Progressive age-related OXPHOS impairment has been described in lymphocytes [7], muscle cells [8] and cardiomyocytes [9].…”