-
Endocrinology Aug 2022Immune cells infiltrate adipose tissue as a function of age, sex, and diet, leading to a variety of regulatory processes linked to metabolic disease and dysfunction....
Immune cells infiltrate adipose tissue as a function of age, sex, and diet, leading to a variety of regulatory processes linked to metabolic disease and dysfunction. Cytokines and chemokines produced by resident macrophages, B cells, T cells and eosinophils play major role(s) in fat cell mitochondrial functions modulating pyruvate oxidation, electron transport and oxidative stress, branched chain amino acid metabolism, fatty acid oxidation, and apoptosis. Indeed, cytokine-dependent downregulation of numerous genes affecting mitochondrial metabolism is strongly linked to the development of the metabolic syndrome, whereas the potentiation of mitochondrial metabolism represents a counterregulatory process improving metabolic outcomes. In contrast, inflammatory cytokines activate mitochondrially linked cell death pathways such as apoptosis, pyroptosis, necroptosis, and ferroptosis. As such, the adipocyte mitochondrion represents a major intersection point for immunometabolic regulation of central metabolism.
Topics: Adipocytes; Adipose Tissue; Cytokines; Mitochondria; Oxidative Stress
PubMed: 35752995
DOI: 10.1210/endocr/bqac094 -
International Journal of Molecular... Aug 2020Mitochondrial stress is considered as a factor that reprograms the mitochondrial biogenesis and metabolism. As known, SUMOylation occurs through a series of... (Review)
Review
Mitochondrial stress is considered as a factor that reprograms the mitochondrial biogenesis and metabolism. As known, SUMOylation occurs through a series of stress-induced biochemical reactions. During the process of SUMOylation, the small ubiquitin-like modifier (SUMO) and its specific proteases (SENPs) are key signal molecules. Furthermore, they are considered as novel mitochondrial stress sensors that respond to the signals produced by various stresses. The responses are critical for mitochondrial homeostasis. The scope of this review is to provide an overview of the function of SUMOylation in the mitochondrial stress response, to delineate a SUMOylation-involved signal network diagram, and to highlight a number of key questions that remain answered.
Topics: Animals; Caloric Restriction; Humans; Mitochondria; Organelle Biogenesis; Stress, Physiological; Sumoylation; Unfolded Protein Response
PubMed: 32781782
DOI: 10.3390/ijms21165657 -
Mitochondrion Jan 2022Iron-sulfur clusters (ISCs) are highly conserved moieties embedded into numerous crucial proteins in almost all bacteria, plants and mammals. As such, ISC biosynthesis... (Review)
Review
Iron-sulfur clusters (ISCs) are highly conserved moieties embedded into numerous crucial proteins in almost all bacteria, plants and mammals. As such, ISC biosynthesis is critical to cellular function. The pathway was first characterized in bacteria by the late 1990s, and over the subsequent 20 years there has been increasing understanding of its components in humans. Defects in the ISC pathway are now associated with many different human disease states, such as Friedreich ataxia and ISCU myopathy. Whilst the disorders have variable clinical features, most involve neurological phenotypes. There are common biochemical signatures in most of these conditions, as a lack of ISCs causes deficiencies of target proteins including Complex I, II and III, aconitase and lipoic acid. This review focuses on the disorders of ISC biogenesis that have been described in the literature to-date. Key clinical, biochemical and neuroradiological features will be discussed, providing a reference point for clinicians diagnosing and managing these patients. Therapies are mostly supportive at this stage. However, the improved understanding of the pathophysiology of these conditions could pave the way for disease-modifying therapies in the near future.
Topics: Animals; Central Nervous System Diseases; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Iron-Sulfur Proteins; Mitochondria
PubMed: 34687937
DOI: 10.1016/j.mito.2021.10.004 -
Chembiochem : a European Journal of... May 2022The mitochondrion is the core site of cell signaling, energy metabolism and biosynthesis. Here, taking advantage of activity-based probes, we synthesized two...
The mitochondrion is the core site of cell signaling, energy metabolism and biosynthesis. Here, taking advantage of activity-based probes, we synthesized two photocontrollable probes (YGH-1 and YGH-2), composed of a mitochondrial localization moiety "triphenylphosphonium", a photo-triggered group to achieve spatially and temporally controlled protein capture, and an alkyne group to enrich the labeled protein. Proteomic validation was further carried out to facilitate identification of the mitochondrial proteome in HeLa cells. The results show that half of the identified protein hits (∼300) labeled by YGH-1 and YGH-2 belong to mitochondria, and are mostly localized in the mitochondrial matrix and inner mitochondrial membrane. Our results provide a new tool for spatial and temporal analysis of subcellular proteomes.
Topics: HeLa Cells; Humans; Mitochondria; Mitochondrial Proteins; Proteome; Proteomics
PubMed: 35344259
DOI: 10.1002/cbic.202200066 -
Cell Reports Dec 2022Nutrient availability regulates the C. elegans life cycle as well as mitochondrial physiology. Food deprivation significantly reduces mitochondrial genome (mtDNA)...
Nutrient availability regulates the C. elegans life cycle as well as mitochondrial physiology. Food deprivation significantly reduces mitochondrial genome (mtDNA) numbers and leads to aging-related phenotypes. Here we show that the bZIP (basic leucine zipper) protein ATFS-1, a mediator of the mitochondrial unfolded protein response (UPR), is required to promote growth and establish a functional germline after prolonged starvation. We find that recovery of mtDNA copy numbers and development after starvation requires mitochondrion-localized ATFS-1 but not its nuclear transcription activity. We also find that the insulin-like receptor DAF-2 functions upstream of ATFS-1 to modulate mtDNA content. We show that reducing DAF-2 activity represses ATFS-1 nuclear function while causing an increase in mtDNA content, partly mediated by mitochondrion-localized ATFS-1. Our data indicate the importance of the UPR in recovering mitochondrial mass and suggest that atfs-1-dependent mtDNA replication precedes mitochondrial network expansion after starvation.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Genome, Mitochondrial; DNA, Mitochondrial; Mitochondria; Unfolded Protein Response
PubMed: 36577367
DOI: 10.1016/j.celrep.2022.111875 -
Mitochondrion Mar 2020
Topics: Energy Metabolism; Homeostasis; Humans; Mitochondria; Mitochondrial Diseases
PubMed: 31917323
DOI: 10.1016/j.mito.2019.12.007 -
Cellular and Molecular Life Sciences :... Apr 2021The ability of a mitochondrion to undergo fission and fusion, and to be transported and localized within a cell are central not just to proper functioning of... (Review)
Review
The ability of a mitochondrion to undergo fission and fusion, and to be transported and localized within a cell are central not just to proper functioning of mitochondria, but also to that of the cell. The cytoskeletal filaments, namely microtubules, F-actin and intermediate filaments, have emerged as prime movers in these dynamic mitochondrial shape and position transitions. In this review, we explore the complex relationship between the cytoskeleton and the mitochondrion, by delving into: (i) how the cytoskeleton helps shape mitochondria via fission and fusion events, (ii) how the cytoskeleton facilitates the translocation and anchoring of mitochondria with the activity of motor proteins, and (iii) how these changes in form and position of mitochondria translate into functioning of the cell.
Topics: Actins; Animals; Cytoskeleton; Humans; Microtubule-Associated Proteins; Microtubules; Mitochondria; Mitochondrial Dynamics; Tubulin
PubMed: 33576841
DOI: 10.1007/s00018-021-03762-5 -
Mitochondrion May 2022Mitochondria are essential for neuronal survival and mitochondrial dysfunction is a hallmark of neurodegeneration. The loss in mitochondrial energy production, oxidative...
Mitochondria are essential for neuronal survival and mitochondrial dysfunction is a hallmark of neurodegeneration. The loss in mitochondrial energy production, oxidative stress, and changes in calcium handling are associated with neurodegenerative diseases; however, different sites and types of mitochondrial dysfunction are linked to distinct neuropathologies. Understanding the causal or correlative relationship between changes in mitochondria and neuropathology will lead to new therapeutic strategies. Here, we summarize the evidence of site-specific mitochondrial dysfunction and mitochondrial-related clinical trials for neurodegenerative diseases. We further discuss potential therapeutic approaches, such as mitochondrial transplantation, restoration of mitochondrial function, and pharmacological alleviation of mitochondrial dysfunction.
Topics: Calcium; Humans; Mitochondria; Neurodegenerative Diseases; Oxidative Stress
PubMed: 35182728
DOI: 10.1016/j.mito.2022.02.004 -
Nano Letters Jul 2021Mitochondrion-targeting therapy exhibits great potential in cancer therapy but significantly suffers from limited therapeutic efficiency. Here we report on...
Mitochondrion-targeting therapy exhibits great potential in cancer therapy but significantly suffers from limited therapeutic efficiency. Here we report on mitochondrion-targeting supramolecular antagonist-inducing tumor cell death via simultaneously promoting cellular apoptosis and preventing survival. The supramolecular antagonist was created via coassembly of a mitochondrion-targeting pentapeptide with its two derivatives functionalized with a BH3 domain or the drug camptothecin (CPT). While drug CPT released from the antagonist induced cellular apoptosis via decreasing the mitochondrial membrane potential, the BH3 domain prevented cellular survival through facilitating the association between the supramolecular antagonists and antiapoptotic proteins, thereby initiating mitochondrial permeabilization. Both and studies confirmed the combinatorial therapeutic effect arising from the BH3 domain and CPT drug within the supramolecular antagonist on cell death and thereby inhibiting tumor growth. Our findings demonstrate an efficient combinatorial mechanism for mitochondrial dysfunction, thus potentially serving as novel organelle-targeting medicines.
Topics: Apoptosis; Camptothecin; Mitochondria
PubMed: 34142834
DOI: 10.1021/acs.nanolett.1c01469 -
Mitochondrion Mar 2021Early-life adversity (ELA), which includes maltreatment, neglect, or severe trauma in childhood, increases the life-long risk for negative health outcomes. Mitochondria...
Early-life adversity (ELA), which includes maltreatment, neglect, or severe trauma in childhood, increases the life-long risk for negative health outcomes. Mitochondria play a key role in the stress response and may be an important mechanism by which stress is transduced into biological risk for disease. By responding to cues from stress-signaling pathways, mitochondria interact dynamically with physiological stress responses coordinated by the central nervous, endocrine, and immune systems. Preclinical evidence suggests that alterations in mitochondrial function and structure are linked to both early stress and systemic biological dysfunction. Early clinical studies support that increased mitochondrial DNA content and altered cellular energy demands may be present in individuals with a history of ELA. Further research should investigate mitochondria as a potential therapeutic target following ELA.
Topics: Adverse Childhood Experiences; Animals; Central Nervous System; Endocrine System; Humans; Immune System; Mitochondria; Stress, Physiological
PubMed: 33484871
DOI: 10.1016/j.mito.2021.01.005