抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Reactive oxygen species and antioxidant machinery in abiotic stress tolerance in crop plants

The production of ROS (reactive oxygen species) by mammalian mitochondria is important because it underlies oxidative damage in many pathologies and contributes to retrograde redox signalling from the organelle to the cytosol and nucleus. Superoxide (O2•−) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O2•− production within the matrix of mammalian mitochondria. The flux of O2•− is related to the concentration of potential electron donors, the local concentration of O2 and the second-order rate constants for the reactions between them. Two modes of operation by isolated mitochondria result in significant O2•− production, predominantly from complex I: (i) when the mitochondria are not making ATP and consequently have a high Δp (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD+ ratio in the mitochondrial matrix. For mitochondria that are actively making ATP, and consequently have a lower Δp and NADH/NAD+ ratio, the extent of O2•− production is far lower. The generation of O2•− within the mitochondrial matrix depends critically on Δp, the NADH/NAD+ and CoQH2/CoQ ratios and the local O2 concentration, which are all highly variable and difficult to measure in vivo. Consequently, it is not possible to estimate O2•− generation by mitochondria in vivo from O2•−-production rates by isolated mitochondria, and such extrapolations in the literature are misleading. Even so, the description outlined here facilitates the understanding of factors that favour mitochondrial ROS production. There is a clear need to develop better methods to measure mitochondrial O2•− and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.

/pdf/how-mitochondria-produce-reactive-oxygen-species-4spvs9r9mw.pdf

How mitochondria produce reactive oxygen species.

### A. Overview

Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cell-surface receptors termed purine receptors. In this review particular emphasis is placed on the discrepancy between the

/pdf/receptors-for-purines-and-pyrimidines-56f78tnpew.pdf

Receptors for Purines and Pyrimidines

Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo.

Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

Brief, intense exercise training may induce metabolic and performance adaptations comparable to traditional endurance training. However, no study has directly compared these diverse training strategies in a standardized manner. We therefore examined changes in exercise capacity and molecular and cellular adaptations in skeletal muscle after low volume sprint-interval training (SIT) and high volume endurance training (ET). Sixteen active men (21 +/- 1 years, ) were assigned to a SIT or ET group (n = 8 each) and performed six training sessions over 14 days. Each session consisted of either four to six repeats of 30 s 'all out' cycling at approximately 250% with 4 min recovery (SIT) or 90-120 min continuous cycling at approximately 65% (ET). Training time commitment over 2 weeks was approximately 2.5 h for SIT and approximately 10.5 h for ET, and total training volume was approximately 90% lower for SIT versus ET ( approximately 630 versus approximately 6500 kJ). Training decreased the time required to complete 50 and 750 kJ cycling time trials, with no difference between groups (main effects, P </= 0.05). Biopsy samples obtained before and after training revealed similar increases in muscle oxidative capacity, as reflected by the maximal activity of cytochrome c oxidase (COX) and COX subunits II and IV protein content (main effects, P </= 0.05), but COX II and IV mRNAs were unchanged. Training-induced increases in muscle buffering capacity and glycogen content were also similar between groups (main effects, P </= 0.05). Given the large difference in training volume, these data demonstrate that SIT is a time-efficient strategy to induce rapid adaptations in skeletal muscle and exercise performance that are comparable to ET in young active men.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2006.112094

Short‐term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance

https://www.cell.com/trends/biochemical-sciences/pdf/S0968-0004(00)01674-1.pdf

Mitochondria, oxygen free radicals, disease and ageing

Reactive oxygen species (ROS) generated by mitochondria are produced as by-products of normal oxidative metabolism. The fate of these species is governed by a number of factors that vary from tissue to tissue in mammals and may be involved in the pathogenesis of disease. Reactive oxygen species are also invoked as agents that are important in the processes which become active in cells undergoing apoptosis. Integration of knowledge surrounding these different aspects of ROS generation is difficult and reveals considerable gaps in our understanding.

Mitochondria, oxygen free radicals, and apoptosis

Superoxides from mitochondrial complex III: the role of manganese superoxide dismutase

The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; female symbol = male symbol). We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.

/pdf/aberrant-mitochondrial-homeostasis-in-the-skeletal-muscle-of-3raogp5gwk.pdf

Sandeep Raha

Papers

Short‐term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance

Mitochondria, oxygen free radicals, disease and ageing

Mitochondria, oxygen free radicals, and apoptosis

Superoxides from mitochondrial complex III: the role of manganese superoxide dismutase

Aberrant Mitochondrial Homeostasis in the Skeletal Muscle of Sedentary Older Adults