Mitochondrial proteins: from biogenesis to functional networks

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(5), P. 267 - 284

Published: Jan. 9, 2019

Language: Английский

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Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches

Frontiers in Oncology, Journal Year: 2019, Volume and Issue: 9

Published: Nov. 1, 2019

Tumor cells must generate sufficient ATP and biosynthetic precursors in order to maintain cell proliferation requirements. Otto Warburg showed that tumor uptake high amounts of glucose producing large volumes lactate even the presence oxygen, this process is known as "Warburg effect or aerobic glycolysis". As a consequence such there an acidification extracellular pH microenvironment, ranging between 6.0-6.5. This acidosis favors processes metastasis, angiogenesis more importantly, immunosuppression, which has been associated worse clinical prognosis. Thus, should be thought important oncometabolite metabolic reprogramming cancer. In review, we summarized role regulating microenvironment cancer discuss its relevance up-regulation enzymes dehydrogenase (LDH) monocarboxilate transporters (MCTs) tumors. The goal review expose not only secondary product cellular waste cells, but also key molecule involved carcinogenesis well immune evasion. Finally, possible targeting production treatment discussed.

Language: Английский

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History and progress of hypotheses and clinical trials for Alzheimer’s disease

Signal Transduction and Targeted Therapy, Journal Year: 2019, Volume and Issue: 4(1)

Published: Aug. 23, 2019

Abstract Alzheimer’s disease (AD) is a neurodegenerative characterized by progressive memory loss along with neuropsychiatric symptoms and decline in activities of daily life. Its main pathological features are cerebral atrophy, amyloid plaques, neurofibrillary tangles the brains patients. There various descriptive hypotheses regarding causes AD, including cholinergic hypothesis, tau propagation mitochondrial cascade calcium homeostasis neurovascular inflammatory metal ion lymphatic system hypothesis. However, ultimate etiology AD remains obscure. In this review, we discuss related clinical trials. Wealthy puzzles lessons have made it possible to develop explanatory theories identify potential strategies for therapeutic interventions AD. The combination hypometabolism autophagy deficiency likely be causative factor We further propose that fluoxetine, selective serotonin reuptake inhibitor, has treat

Language: Английский

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The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 66, P. 101249 - 101249

Published: Dec. 29, 2020

Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and high levels of clinical heterogeneity. Aberrant chondrocyte metabolism response to changes in the inflammatory microenvironment may play key role cartilage degeneration OA progression. Under conditions environmental stress, chondrocytes tend adapt their microenvironmental shifting from one metabolic pathway another, for example oxidative phosphorylation glycolysis. Similar occur other cells, including synoviocytes. Switching between these pathways implicated alterations that involve mitochondrial dysfunction, enhanced anaerobic glycolysis, altered lipid amino acid metabolism. The shift glycolysis mainly regulated AMP-activated protein kinase (AMPK) mechanistic target rapamycin (mTOR) pathways. Chondrocyte are likely be feature different phenotypes. Determining has revealed features pathogenesis. Future research should place greater emphasis on immunometabolism as means understand pathophysiology age-related OA. This knowledge will advance development new drugs against therapeutic targets significance.

Language: Английский

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Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions

Molecules, Journal Year: 2018, Volume and Issue: 23(2), P. 509 - 509

Published: Feb. 24, 2018

Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or exposed toxins. Oxidative damage is a result free radicals produced in cells, especially mitochondria. When measured, melatonin, potent antioxidant, was found be higher concentrations mitochondria than other organelles subcellular locations. Recent evidence indicates that mitochondrial membranes possess transporters aid rapid uptake melatonin by these against gradient. Moreover, we predicted several years ago that, because their origin from melatonin-producing bacteria, likely also synthesize melatonin. Data accumulated within last year supports this prediction. A high content would fortuitous, since produce an abundance radicals. Thus, optimally positioned scavenge and degree damage. In light “free radical theory aging”, including all iterations, levels expected protect age-related organismal decline. Also, there are many age-associated diseases have, as contributing factor, These multiple may deferred onset progression if can maintained into advanced age.

Language: Английский

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OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis elegans Genes

Genetics, Journal Year: 2018, Volume and Issue: 210(2), P. 445 - 461

Published: Aug. 17, 2018

Abstract OrthoList, a compendium of Caenorhabditis elegans genes with human orthologs compiled in 2011 by meta-analysis four orthology-prediction methods, has been popular tool for identifying conserved research into biological and disease mechanisms. However, the efficacy orthology prediction depends on accuracy gene-model predictions, an ongoing process, algorithms have also updated over time. Here we present OrthoList 2 (OL2), new comparative genomic analysis between C. humans, first assessment how changes time affect landscape predicted two species. Although find that updates to methods significantly changed elegans–human individual programs and—unexpectedly—reduced agreement among them, show our approach “buffered” against gene content. We adding results from more did not lead many additions list discuss reasons avoid assigning “scores” based support programs; treatment “legacy” no longer these practical difficulties updating due encountering deprecated, changed, or retired identifiers. In addition, consider what other criteria may claims alternative approaches potential elude identification programs. Finally, created web-based allows rapid searches OL2 identifiers, protein domains [InterPro SMART (Simple Modular Architecture Research Tool], associations ([OMIM (Online Mendelian Inheritence Man], includes available RNA-interference resources facilitate translational cross-species studies.

Language: Английский

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Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context

Cell Metabolism, Journal Year: 2021, Volume and Issue: 33(12), P. 2464 - 2483.e18

Published: Nov. 19, 2021

Mitochondria are key organelles for cellular energetics, metabolism, signaling, and quality control have been linked to various diseases. Different views exist on the composition of human mitochondrial proteome. We classified >8,000 proteins in preparations cells defined a high-confidence proteome >1,100 (MitoCoP). identified interactors translocases, respiratory chain, ATP synthase assembly factors. The abundance MitoCoP covers six orders magnitude amounts 7% with chaperones HSP60-HSP10 being most abundant proteins. dynamics spans three magnitudes, half-lives from hours months, suggests rapid regulation biosynthesis processes. 460 genes diseases strong prevalence central nervous system metabolism. will provide resource placing dynamics, functions, dysfunctions mitochondria into context.

Language: Английский

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mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer

Frontiers in Oncology, Journal Year: 2019, Volume and Issue: 9

Published: Dec. 13, 2019

Continuous proliferation of tumor cells require many adjustments energy metabolism to rapidly fuel cell growth and division. This energetic reprogramming often comprises deregulated glucose uptake lactate production in the presence oxygen, a process known as "Warburg effect". For years it was thought that Warburg effect result mitochondrial damage however, unlike this proposal, mitochondria not only retain their functionality, but also instrumental for integrating variety signals adjusting metabolic activity cell. The mammalian/mechanistic target rapamycin complex 1 (mTORC1) is master regulator numerous cellular processes implicated growth. mTORC1 controls mainly by regulating translation transcription genes. Here we present an overview on role regulation functions cancer, considering new evidences showing regulates nucleus-encoded mRNAs increased ATP production. Moreover, discuss relationship between glutaminolysis, well metabolites. In addition, fission regulated its impact cancer are discussed. We finally review therapeutic efficacy inhibitors treatments, use combination with other drugs, particular metabolism, could help improve anti neoplastic eliminate patients.

Language: Английский

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Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Aug. 27, 2020

Older organs represent an untapped potential to close the gap between demand and supply in organ transplantation but are associated with age-specific responses injury increased immunogenicity, thereby aggravating transplant outcomes. Here we show that cell-free mitochondrial DNA (cf-mt-DNA) released by senescent cells accumulates aging augments immunogenicity. Ischemia reperfusion induces a systemic increase of cf-mt-DNA promotes dendritic cell-mediated, inflammatory responses. Comparable events observed clinically, levels elevated older deceased donors, isolated capable activating human cells. In experimental models, treatment old donor animals senolytics clear diminish release, dampening immune prolonging survival cardiac allografts comparable young organs. Collectively, identify accumulating as key factor inflamm-aging present approach improve outcomes availability.

Language: Английский

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Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Dec. 18, 2020

Abstract Acute myeloid leukemia (AML) is the most common form of acute in adults and second children. Despite this, very little improvement survival rates has been achieved over past few decades. This partially due to heterogeneity AML need for more targeted therapeutics than traditional cytotoxic chemotherapies that have a mainstay therapy 50 years. In 20 years, research diversifying approach treating by investigating molecular pathways uniquely relevant cell proliferation survival. Here we review development novel targeting apoptosis, receptor tyrosine kinase (RTK) signaling, hedgehog (HH) pathway, mitochondrial function, DNA repair, c-Myc signaling. There an impressive effort into better understanding diversity characteristics here highlight important preclinical studies supported therapeutic continue promote new ways target cells. addition, describe clinical investigations led FDA approval therapies ongoing trials pathways. We also complexity stem cells (LSCs) as addressing relapse remission targetable are unique LSC comprehensive details what currently understand about signaling support exceptional which disrupt them.

Language: Английский

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