Mitochondrial form, function and signalling in aging

2016 ◽  
Vol 473 (20) ◽  
pp. 3421-3449 ◽  
Author(s):  
Ignacio Amigo ◽  
Fernanda M. da Cunha ◽  
Maria Fernanda Forni ◽  
Wilson Garcia-Neto ◽  
Pâmela A. Kakimoto ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Energy Homeostasis ◽  
Cell Types ◽  
Redox Balance ◽  
Whole Body ◽  
Model Organisms ◽  
Resistance To Stress ◽  
Whole Body Metabolism ◽  
And Function ◽  
Different Characteristics

Aging is often accompanied by a decline in mitochondrial mass and function in different tissues. Additionally, cell resistance to stress is frequently found to be prevented by higher mitochondrial respiratory capacity. These correlations strongly suggest mitochondria are key players in aging and senescence, acting by regulating energy homeostasis, redox balance and signalling pathways central in these processes. However, mitochondria display a wide array of functions and signalling properties, and the roles of these different characteristics are still widely unexplored. Furthermore, differences in mitochondrial properties and responses between tissues and cell types, and how these affect whole body metabolism are also still poorly understood. This review uncovers aspects of mitochondrial biology that have an impact upon aging in model organisms and selected mammalian cells and tissues.

β-Arrestins as Important Regulators of Glucose and Energy Homeostasis

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Sai P. Pydi ◽  
Luiz F. Barella ◽  
Lu Zhu ◽  
Jaroslawna Meister ◽  
Mario Rossi ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Cell Types ◽  
Mutant Mice ◽  
Whole Body ◽  
Annual Review ◽  
Publication Date ◽  
Cytoplasmic Proteins ◽  
New Findings ◽  
Novel Drugs ◽  
G Protein Coupled

β-Arrestin-1 and -2 (also known as arrestin-2 and -3, respectively) are ubiquitously expressed cytoplasmic proteins that dampen signaling through G protein–coupled receptors. However, β-arrestins can also act as signaling molecules in their own right. To investigate the potential metabolic roles of the two β-arrestins in modulating glucose and energy homeostasis, recent studies analyzed mutant mice that lacked or overexpressed β-arrestin-1 and/or -2 in distinct, metabolically important cell types. Metabolic analysis of these mutant mice clearly demonstrated that both β-arrestins play key roles in regulating the function of most of these cell types, resulting in striking changes in whole-body glucose and/or energy homeostasis. These studies also revealed that β-arrestin-1 and -2, though structurally closely related, clearly differ in their metabolic roles under physiological and pathophysiological conditions. These new findings should guide the development of novel drugs for the treatment of various metabolic disorders, including type 2 diabetes and obesity. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Subcellular Specialization of Mitochondrial Form and Function in Skeletal Muscle Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
T. Bradley Willingham ◽  
Peter T. Ajayi ◽  
Brian Glancy
Keyword(s):  
Skeletal Muscle ◽  
Energy Homeostasis ◽  
Single Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Current Data ◽  
Skeletal Muscle Cells ◽  
Form And Function ◽  
Mitochondrial Heterogeneity ◽  
And Function

Across different cell types and within single cells, mitochondria are heterogeneous in form and function. In skeletal muscle cells, morphologically and functionally distinct subpopulations of mitochondria have been identified, but the mechanisms by which the subcellular specialization of mitochondria contributes to energy homeostasis in working muscles remains unclear. Here, we discuss the current data regarding mitochondrial heterogeneity in skeletal muscle cells and highlight potential new lines of inquiry that have emerged due to advancements in cellular imaging technologies.

scholarly journals The Impact of Single-Cell Genomics on Adipose Tissue Research

2020 ◽  
Vol 21 (13) ◽  
pp. 4773
Author(s):  
Alana Deutsch ◽  
Daorong Feng ◽  
Jeffrey E. Pessin ◽  
Kosaku Shinoda
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Diabetes Research ◽  
Obesity And Diabetes ◽  
Important Regulator ◽  
Whole Body Metabolism ◽  
Tissue Aging ◽  
The Impact

Adipose tissue is an important regulator of whole-body metabolism and energy homeostasis. The unprecedented growth of obesity and metabolic disease worldwide has required paralleled advancements in research on this dynamic endocrine organ system. Single-cell RNA sequencing (scRNA-seq), a highly meticulous methodology used to dissect tissue heterogeneity through the transcriptional characterization of individual cells, is responsible for facilitating critical advancements in this area. The unique investigative capabilities achieved by the combination of nanotechnology, molecular biology, and informatics are expanding our understanding of adipose tissue’s composition and compartmentalized functional specialization, which underlie physiologic and pathogenic states, including adaptive thermogenesis, adipose tissue aging, and obesity. In this review, we will summarize the use of scRNA-seq and single-nuclei RNA-seq (snRNA-seq) in adipocyte biology and their applications to obesity and diabetes research in the hopes of increasing awareness of the capabilities of this technology and acting as a catalyst for its expanded use in further investigation.

scholarly journals Signals from the Circle: Tricarboxylic Acid Cycle Intermediates as Myometabokines

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 474
Author(s):  
Jennifer Maurer ◽  
Miriam Hoene ◽  
Cora Weigert
Keyword(s):  
Skeletal Muscle ◽  
Tricarboxylic Acid Cycle ◽  
Cell Types ◽  
Tricarboxylic Acid ◽  
Muscle Performance ◽  
Whole Body ◽  
Small Proteins ◽  
Exercise Adaptation ◽  
Whole Body Metabolism ◽  
Adaptation Processes

Regular physical activity is an effective strategy to prevent and ameliorate aging-associated diseases. In particular, training increases muscle performance and improves whole-body metabolism. Since exercise affects the whole organism, it has countless health benefits. The systemic effects of exercise can, in part, be explained by communication between the contracting skeletal muscle and other organs and cell types. While small proteins and peptides known as myokines are the most prominent candidates to mediate this tissue cross-talk, recent investigations have paid increasing attention to metabolites. The purpose of this review is to highlight the potential role of tricarboxylic acid (TCA) metabolites as humoral mediators of exercise adaptation processes. We focus on TCA metabolites that are released from human skeletal muscle in response to exercise and provide an overview of their potential auto-, para- or endocrine health-promoting effects.

scholarly journals Lactate Fluxes and Plasticity of Adipose Tissues: A Redox Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Damien Lagarde ◽  
Yannick Jeanson ◽  
Jean-Charles Portais ◽  
Anne Galinier ◽  
Isabelle Ader ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Biological Effects ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Whole Body ◽  
Glycolytic Flux ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Wide Range

Lactate, a metabolite produced when the glycolytic flux exceeds mitochondrial oxidative capacities, is now viewed as a critical regulator of metabolism by acting as both a carbon and electron carrier and a signaling molecule between cells and tissues. In recent years, increasing evidence report its key role in white, beige, and brown adipose tissue biology, and highlights new mechanisms by which lactate participates in the maintenance of whole-body energy homeostasis. Lactate displays a wide range of biological effects in adipose cells not only through its binding to the membrane receptor but also through its transport and the subsequent effect on intracellular metabolism notably on redox balance. This study explores how lactate regulates adipocyte metabolism and plasticity by balancing intracellular redox state and by regulating specific signaling pathways. We also emphasized the contribution of adipose tissues to the regulation of systemic lactate metabolism, their roles in redox homeostasis, and related putative physiopathological repercussions associated with their decline in metabolic diseases and aging.

Identification of a 40 × 10(3) Mr centromere-associated protein in cultured mammalian cells

1990 ◽  
Vol 97 (4) ◽  
pp. 705-713
Author(s):  
R. Balczon ◽  
M.A. Accavitti ◽  
B.R. Brinkley
Keyword(s):  
Mammalian Cells ◽  
Cell Types ◽  
Immunoblot Analysis ◽  
Structure And Function ◽  
Interphase Nuclei ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
Cytoplasmic Microtubules ◽  
And Function

Monoclonal antibodies were raised against a complex of proteins that was purified following the crosslinking of tubulin to the centromeres of CHO chromosomes using Lomant's reagent. One of the clones, hybridoma 32–9, produced antibodies that reacted with a 40 × 10(3) Mr protein present in the crosslinked complex. Furthermore, immunoblot analysis demonstrated that the 40 × 10(3) Mr antigen was present in various mammalian cell types from several different species. Indirect immunofluorescence using the antibody produced by clone 32–9 demonstrated that the 40 × 10(3) Mr antigen was associated with both spindle and cytoplasmic microtubules. In addition, centromere/kinetochore staining was detected in metaphase-arrested cells, while staining of prekinetochores in interphase nuclei was not observed. Unlike microtubule-associated proteins and microtubule-dependent ATPases, the 40 × 10(3) Mr protein did not copurify with microtubules when tubules were assembled from cellular homogenates using taxol and either GTP or GTP and AMP-PNP. Instead, the 40 × 10(3) Mr protein remained associated with the insoluble cellular material. The 40 × 10(3) Mr antigen could be released from the insoluble pelleted material by extraction with 1 M NaCl. Once solubilized, the 40 × 10(3) Mr protein was able to copurify with microtubules in assembly assays in vitro. This monoclonal antibody should serve as a valuable probe for studies of centromere/kinetochore structure and function.

scholarly journals Agrp-Specific Ablation of Scly Protects against Diet-Induced Obesity and Leptin Resistance

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1693 ◽  
Author(s):  
Daniel J. Torres ◽  
Matthew W. Pitts ◽  
Ann C. Hashimoto ◽  
Marla J. Berry
Keyword(s):  
Knockout Mice ◽  
Energy Homeostasis ◽  
Leptin Resistance ◽  
Whole Body ◽  
Metabolism Regulation ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Brown Adipose ◽  
Whole Body Metabolism

Selenium, an essential trace element known mainly for its antioxidant properties, is critical for proper brain function and regulation of energy metabolism. Whole-body knockout of the selenium recycling enzyme, selenocysteine lyase (Scly), increases susceptibility to metabolic syndrome and diet-induced obesity in mice. Scly knockout mice also have decreased selenoprotein expression levels in the hypothalamus, a key regulator of energy homeostasis. This study investigated the role of selenium in whole-body metabolism regulation using a mouse model with hypothalamic knockout of Scly. Agouti-related peptide (Agrp) promoter-driven Scly knockout resulted in reduced weight gain and adiposity while on a high-fat diet (HFD). Scly-Agrp knockout mice had reduced Agrp expression in the hypothalamus, as measured by Western blot and immunohistochemistry (IHC). IHC also revealed that while control mice developed HFD-induced leptin resistance in the arcuate nucleus, Scly-Agrp knockout mice maintained leptin sensitivity. Brown adipose tissue from Scly-Agrp knockout mice had reduced lipid deposition and increased expression of the thermogenic marker uncoupled protein-1. This study sheds light on the important role of selenium utilization in energy homeostasis, provides new information on the interplay between the central nervous system and whole-body metabolism, and may help identify key targets of interest for therapeutic treatment of metabolic disorders.

scholarly journals Matrix metalloproteinase 11 protects from diabesity and promotes metabolic switch

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Nassim Dali-Youcef ◽  
Karim Hnia ◽  
Sébastien Blaise ◽  
Nadia Messaddeq ◽  
Stéphane Blanc ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Energy Homeostasis ◽  
Aerobic Glycolysis ◽  
Whole Body ◽  
Metabolic Switch ◽  
Metabolic Signalling ◽  
Cancer Cell Survival ◽  
Whole Body Metabolism

Abstract MMP11 overexpression is a bad prognostic factor in various human carcinomas. Interestingly, this proteinase is not expressed in malignant cells themselves but is secreted by adjacent non-malignant mesenchymal/stromal cells, such as cancer associated fibroblasts (CAFs) and adipocytes (CAAs), which favors cancer cell survival and progression. As MMP11 negatively regulates adipogenesis in vitro, we hypothesized that it may play a role in whole body metabolism and energy homeostasis. We used an in vivo gain- (Mmp11-Tg mice) and loss- (Mmp11−/− mice) of-function approach to address the systemic function of MMP11. Strikingly, MMP11 overexpression protects against type 2 diabetes while Mmp11−/− mice exhibit hallmarks of metabolic syndrome. Moreover, Mmp11-Tg mice were protected from diet-induced obesity and display mitochondrial dysfunction, due to oxidative stress, and metabolic switch from oxidative phosphorylation to aerobic glycolysis. This Warburg-like effect observed in adipose tissues might provide a rationale for the deleterious impact of CAA-secreted MMP11, favouring tumor progression. MMP11 overexpression also leads to increased circulating IGF1 levels and the activation of the IGF1/AKT/FOXO1 cascade, an important metabolic signalling pathway. Our data reveal a major role for MMP11 in controlling energy metabolism, and provide new clues for understanding the relationship between metabolism, cancer progression and patient outcome.

scholarly journals Optical volume and mass measurements show that mammalian cells swell during mitosis

2015 ◽  
Vol 211 (4) ◽  
pp. 765-774 ◽  
Author(s):  
Ewa Zlotek-Zlotkiewicz ◽  
Sylvain Monnier ◽  
Giovanni Cappello ◽  
Mael Le Berre ◽  
Matthieu Piel
Keyword(s):  
Mammalian Cells ◽  
Large Change ◽  
Cell Types ◽  
Dry Mass ◽  
Mitotic Progression ◽  
Mass Measurements ◽  
Volume Increase ◽  
Cellular Events ◽  
And Function ◽  
Mitotic Cells

The extent, mechanism, and function of cell volume changes during specific cellular events, such as cell migration and cell division, have been poorly studied, mostly because of a lack of adequate techniques. Here we unambiguously report that a large range of mammalian cell types display a significant increase in volume during mitosis (up to 30%). We further show that this increase in volume is tightly linked to the mitotic state of the cell and not to its spread or rounded shape and is independent of the presence of an intact actomyosin cortex. Importantly, this volume increase is not accompanied by an increase in dry mass and thus corresponds to a decrease in cell density. This mitotic swelling might have important consequences for mitotic progression: it might contribute to produce strong pushing forces, allowing mitotic cells to round up; it might also, by lowering cytoplasmic density, contribute to the large change of physicochemical properties observed in mitotic cells.

scholarly journals The regulation and function of the NUAK family

2013 ◽  
Vol 51 (2) ◽  
pp. R15-R22 ◽  
Author(s):  
Xianglan Sun ◽  
Ling Gao ◽  
Hung-Yu Chien ◽  
Wan-Chun Li ◽  
Jiajun Zhao
Keyword(s):  
Protein Kinase ◽  
Structural Organization ◽  
Energy Homeostasis ◽  
Catalytic Domain ◽  
Whole Body ◽  
Upstream Kinase ◽  
Liver Kinase B1 ◽  
And Function ◽  
Amp Activated Protein Kinase ◽  
Body Energy

AMP-activated protein kinase (AMPK) is a critical regulator of cellular and whole-body energy homeostasis. Twelve AMPK-related kinases (ARKs; BRSK1, BRSK2, NUAK1, NUAK2, QIK, QSK, SIK, MARK1, MARK2, MARK3, MARK4, and MELK) have been identified recently. These kinases show a similar structural organization, including an N-terminal catalytic domain, followed by a ubiquitin-associated domain and a C-terminal spacer sequence, which in some cases also contains a kinase-associated domain 1. Eleven of the ARKs are phosphorylated and activated by the master upstream kinase liver kinase B1. However, most of these ARKs are largely unknown, and the NUAK family seems to have different regulations and functions. This review contains a brief discussion of the NUAK family including the specific characteristics of NUAK1 and NUAK2.

Sign in / Sign up

Export Citation Format

Share Document