Mitochondrial-derived peptides in energy metabolism

Merry, Troy L.; Chan, Alex; Woodhead, Jonathan S T; Reynolds, Joseph; Kumagai, Hiroshi; Kim, Su-Jeong; Lee, Changhan

doi:10.1152/ajpendo.00249.2020

Cited by 93 publications

(69 citation statements)

References 58 publications

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“…Such regulatory age-determined signaling from mitochondrion to nucleus, lying at the nexus of metabolic regulation, has been neatly demonstrated for replicative aging in yeast [ 48 ]. Interestingly, an important role in retrograde signaling was ascribed to mitochondria-generated peptides [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Age-Related Changes in Bone-Marrow Mesenchymal Stem Cells

Babenko

Silachev

Danilina

et al. 2021

Cells

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The use of stem cells is part of a strategy for the treatment of a large number of diseases. However, the source of the original stem cells for use is extremely important and determines their therapeutic potential. Mesenchymal stromal cells (MSC) have proven their therapeutic effectiveness when used in a number of pathological models. However, it remains an open question whether the chronological age of the donor organism affects the effectiveness of the use of MSC. The asymmetric division of stem cells, the result of which is some residential stem cells acquiring a non-senile phenotype, means that stem cells possess an intrinsic ability to preserve juvenile characteristics, implying an absence or at least remarkable retardation of senescence in stem cells. To test whether residential MSC senesce, we evaluated the physiological changes in the MSC from old rats, with a further comparison of the neuroprotective properties of MSC from young and old animals in a model of traumatic brain injury. We found that, while the effect of administration of MSC on lesion volume was minimal, functional recovery was remarkable, with the highest effect assigned to fetal cells; the lowest effect was recorded for cells isolated from adult rats and postnatal cells, having intermediate potency. MSC from the young rats were characterized by a faster growth than adult MSC, correlating with levels of proliferating cell nuclear antigen (PCNA). However, there were no differences in respiratory activity of MSC from young and old rats, but young cells showed much higher glucose utilization than old ones. Autophagy flux was almost the same in both types of cells, but there were remarkable ultrastructural differences in old and young cells.

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Section: Discussionmentioning

confidence: 99%

Age-Related Changes in Bone-Marrow Mesenchymal Stem Cells

Babenko

Silachev

Danilina

et al. 2021

Cells

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“…Our ndings are consistent with previous studies that have identi ed a relationship between MDPs and insulin resistance. There is evidence of the insulin-sensitizing properties of MDPs mainly derived from cellular and animal models [11]. MOTSc is detected in the circulation, and its target organs are primarily skeletal muscle and fat.…”

Section: Discussionmentioning

confidence: 99%

Evolution of Mitochondrial-Derived Peptides, Humanin and MOTSc and Changes in Insulin Sensitivity During Early Gestation

Ruiz¹,

Santibáñez²,

Alio-Lavín³

et al. 2021

Preprint

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Aims: To study the evolution of mitochondrial-derived peptides (MDPs) and their relationship with changes in insulin sensitivity from the early stages of pregnancy.Methods: MDPs (humanin and MOTSc) were assessed in the first and second trimesters of gestation in 28 pregnant women with gestational diabetes mellitus (GDM) and a subgroup of 45 matched pregnant women without GDM. Insulin resistance (IR) was defined as a HOMA-IR index ≥70 percentile.Results: We observed a significant reduction in both humanin and MOTSc levels from the first to the second trimesters of pregnancy. After adjusting for BMI we did not find an association between low levels of humanin and the occurrence of a high HOMA-IR index (adjusted OR= 2.63 and 3.14, linear p-trend 0.260 and 0.175, respectively). Regarding MOTSc, an association was found only for the second trimester: adjusted OR=7.68 (95% CI 1.49-39.67), linear p-trend=0.012. No significant associations were observed in humanin change with insulin resistance throughout pregnancy, but changes in MOTSc levels were significantly associated with HOMA-IR index: adjusted OR 3.73 (95% CI 1.03-13.50).Conclusions: MOTSc levels, especially a strong decrease from the first to the second trimester of gestation, may be involved in increasing insulin resistance during early gestation.CLINICAL TRIAL REGISTRATIONNot applicable

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“…Localization of many coding and non-coding RNA, components of these granules, demonstrates complex dynamics [ 187 , 188 ]. It is curious that the granules are also associated with the mitochondrial ribosomal RNA, which is found at this moment in the cytoplasm [ 189 , 190 ] and can be translated [ 191 ]. The complex pattern and dynamics of mRNA distribution seem to provide regulation of translation during the maturation of germ cells and in the early stages of embryogenesis [ 185 ].…”

Section: Cytosolic Ribonucleoprotein Granules and “Translation Factormentioning

confidence: 99%

mRNA Targeting, Transport and Local Translation in Eukaryotic Cells: From the Classical View to a Diversity of New Concepts

Lashkevich

Dmitriev

2021

Mol Biol

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Spatial organization of protein biosynthesis in the eukaryotic cell has been studied for more than fifty years, thus many facts have already been included in textbooks. According to the classical view, mRNA transcripts encoding secreted and transmembrane proteins are translated by ribosomes associated with endoplasmic reticulum membranes, while soluble cytoplasmic proteins are synthesized on free polysomes. However, in the last few years, new data has emerged, revealing selective translation of mRNA on mitochondria and plastids, in proximity to peroxisomes and endosomes, in various granules and at the cytoskeleton (actin network, vimentin intermediate filaments, microtubules and centrosomes). There are also long-standing debates about the possibility of protein synthesis in the nucleus. Localized translation can be determined by targeting signals in the synthesized protein, nucleotide sequences in the mRNA itself, or both. With RNA-binding proteins, many transcripts can be assembled into specific RNA condensates and form RNP particles, which may be transported by molecular motors to the sites of active translation, form granules and provoke liquid-liquid phase separation in the cytoplasm, both under normal conditions and during cell stress. The translation of some mRNAs occurs in specialized “translation factories,” assemblysomes, transperons and other structures necessary for the correct folding of proteins, interaction with functional partners and formation of oligomeric complexes. Intracellular localization of mRNA has a significant impact on the efficiency of its translation and presumably determines its response to cellular stress. Compartmentalization of mRNAs and the translation machinery also plays an important role in viral infections. Many viruses provoke the formation of specific intracellular structures, virus factories, for the production of their proteins. Here we review the current concepts of the molecular mechanisms of transport, selective localization and local translation of cellular and viral mRNAs, their effects on protein targeting and topogenesis, and on the regulation of protein biosynthesis in different compartments of the eukaryotic cell. Special attention is paid to new systems biology approaches, providing new cues to the study of localized translation.

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Mitochondrial-derived peptides in energy metabolism

Cited by 93 publications

References 58 publications

Age-Related Changes in Bone-Marrow Mesenchymal Stem Cells

Age-Related Changes in Bone-Marrow Mesenchymal Stem Cells

Evolution of Mitochondrial-Derived Peptides, Humanin and MOTSc and Changes in Insulin Sensitivity During Early Gestation

mRNA Targeting, Transport and Local Translation in Eukaryotic Cells: From the Classical View to a Diversity of New Concepts

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