bims-misrem 2020-12-27 papers

Mitochondrion. 2020 Dec 16. pii: S1567-7249(20)30226-9. [Epub ahead of print]

Alterations in Inter-organelle Crosstalk and Ca2+ Signaling through Mitochondria during Proteotoxic Stresses.

Mudassar Ali, Kannan Boosi Narayana Rao, Priyanka Majumder, Rajasri Sarkar, Koyeli Mapa.

BACKGROUND: Biogenesis and function of mitochondria is profoundly dependent on cytosolic translation of mitochondrial pre-proteins and its subsequent translocation and folding inside the organelle. Continuous exposure of non-native precursor proteins, exposure to damaging by-products of oxidative phosphorylation, load of mis-targeted or misfolded proteins from neighbouring compartments and unremitting demand of communication between mitochondrial and nuclear genomes, continuously pose proteotoxic threats to the organelle. Our knowledge of cellular mechanisms to cope up with such impending threat of proteotoxicity to mitochondria, is currently evolving. In recent years, several unique response and survival pathways have been discovered shedding light on cellular strategies to cope with stressed and dysfunctional mitochondria. As mitochondria compulsorily communicate with nucleus, cytosol and endoplasmic reticulum (ER) for its own biogenesis and function and in turn maintain critical cellular processes for survival, any impairment in communication by stressed or dysfunctional mitochondria may end up with fatal consequences.
DISCUSSION: and Implication: In this review, we have discussed about possible sources of mitochondrial proteotoxicity and the recent developments regarding cellular strategies to counter such stress to overcome dysfunctions of the organelle. Mitochondrial communication with neighbouring subcellular compartments like ER and cytosol during proteotoxic stress have been explored. In the context of mitochondrial proteotoxicity, alterations of crucial inter-organelle connections like ER-mitochondria contact sites and its implication on mitochondrial signaling activity like Ca2+ signaling have been dissected. Furthermore, an overview of pathological conditions, mainly neurodegenerative disorders that are known to be associated with mitochondrial proteotoxicity and Ca2+ dysregulation has been presented.

Keywords: Apoptosis; Ca(2+) signaling; Mitochondria; Mitochondria associated ER-membranes (MAMs); Proteotoxic Stress; Unfolded Protein Response (UPR)

DOI: https://doi.org/10.1016/j.mito.2020.12.003

J Cachexia Sarcopenia Muscle. 2020 Dec 21.

The effect of short-term exercise prehabilitation on skeletal muscle protein synthesis and atrophy during bed rest in older men.

Benoit Smeuninx, Yasir S Elhassan, Konstantinos N Manolopoulos, Elizabeth Sapey, Alison B Rushton, Sophie J Edwards, Paul T Morgan, Andrew Philp, Matthew S Brook, Nima Gharahdaghi, Kenneth Smith, Philip J Atherton, Leigh Breen.

BACKGROUND: Poor recovery from periods of disuse accelerates age-related muscle loss, predisposing individuals to the development of secondary adverse health outcomes. Exercise prior to disuse (prehabilitation) may prevent muscle deterioration during subsequent unloading. The present study aimed to investigate the effect of short-term resistance exercise training (RET) prehabilitation on muscle morphology and regulatory mechanisms during 5 days of bed rest in older men.
METHODS: Ten healthy older men aged 65-80 years underwent four bouts of high-volume unilateral leg RET over 7 days prior to 5 days of inpatient bed rest. Physical activity and step-count were monitored over the course of RET prehabilitation and bed rest, whilst dietary intake was recorded throughout. Prior to and following bed rest, quadriceps cross-sectional area (CSA), and hormone/lipid profiles were determined. Serial muscle biopsies and dual-stable isotope tracers were used to determine integrated myofibrillar protein synthesis (iMyoPS) over RET prehabilitation and bed rest phases, and acute postabsorptive and postprandial myofibrillar protein synthesis (aMyoPS) rates at the end of bed rest.
RESULTS: During bed rest, daily step-count and light and moderate physical activity time decreased, whilst sedentary time increased when compared with habitual levels (P < 0.001 for all). Dietary protein and fibre intake during bed rest were lower than habitual values (P < 0.01 for both). iMyoPS rates were significantly greater in the exercised leg (EX) compared with the non-exercised control leg (CTL) over prehabilitation (1.76 ± 0.37%/day vs. 1.36 ± 0.18%/day, respectively; P = 0.007). iMyoPS rates decreased similarly in EX and CTL during bed rest (CTL, 1.07 ± 0.22%/day; EX, 1.30 ± 0.38%/day; P = 0.037 and 0.002, respectively). Postprandial aMyoPS rates increased above postabsorptive values in EX only (P = 0.018), with no difference in delta postprandial aMyoPS stimulation between legs. Quadriceps CSA at 40%, 60%, and 80% of muscle length decreased significantly in EX and CTL over bed rest (0.69%, 3.5%, and 2.8%, respectively; P < 0.01 for all), with no differences between legs. No differences in fibre-type CSA were observed between legs or with bed rest. Plasma insulin and serum lipids did not change with bed rest.
CONCLUSION: Short-term resistance exercise prehabilitation augmented iMyoPS rates in older men but did not offset the relative decline in iMyoPS and muscle mass during bed rest.

Keywords: Bed rest; Muscle; Protein synthesis; Sarcopenia

DOI: https://doi.org/10.1002/jcsm.12661

Ageing Res Rev. 2020 Dec 16. pii: S1568-1637(20)30372-X. [Epub ahead of print] 101237

Pleiotropic effects of alpha-ketoglutarate as a potential anti-ageing agent.

Maria M Bayliak, Volodymyr I Lushchak.

An intermediate of tricarboxylic acid cycle alpha-ketoglutarate (AKG) is involved in pleiotropic metabolic and regulatory pathways in the cell, including energy production, biosynthesis of certain amino acids, collagen biosynthesis, epigenetic regulation of gene expression, regulation of redox homeostasis, and detoxification of hazardous substances. Recently, AKG supplement was found to extend lifespan and delay the onset of age-associated decline in experimental models such as nematodes, fruit flies, yeasts, and mice. This review summarizes current knowledge on metabolic and regulatory functions of AKG and its potential anti-ageing effects. Impact on epigenetic regulation of ageing via being an obligate substrate of DNA and histone demethylases, direct antioxidant properties, and function as mimetic of caloric restriction and hormesis-induced agent are among proposed mechanisms of AKG geroprotective action. Due to influence on mitochondrial respiration, AKG can stimulate production of reactive oxygen species (ROS) by mitochondria. According to hormesis hypothesis, moderate stimulation of ROS production could have rather beneficial biological effects, than detrimental ones, because of the induction of defensive mechanisms that improve resistance to stressors and age-related diseases and slow down functional senescence. Discrepancies found in different models and limitations of AKG as a geroprotective drug are discussed.

Keywords: TCA cycle; antioxidant; collagen; epigenetics; hormesis; stress resistance

DOI: https://doi.org/10.1016/j.arr.2020.101237

Cell Calcium. 2020 Dec 08. pii: S0143-4160(20)30171-8. [Epub ahead of print]93 102329

Lactate as a new second messenger shaping intracellular Mg2+ dynamics and bioenergetics.

Vladimir Chubanov, Thomas Gudermann.

Mg2+ is an essential cation controlling many biochemical reactions. Recently, Daw et al. [1] have shown that l-lactate acts as a second messenger triggering a dynamic exchange of Mg2+ between the endoplasmic reticulum and mitochondria to shape energy metabolism. This discovery changes our view on the cellular role of Mg2+.

Keywords: Bioenergetics; Lactate; Mg(2+); Mitochondria; Mrs2

DOI: https://doi.org/10.1016/j.ceca.2020.102329