Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction

Nature Metabolism, Год журнала: 2023, Номер 5(4), С. 546 - 562

Опубликована: Апрель 26, 2023

Язык: Английский

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Origin of Antibiotics and Antibiotic Resistance, and Their Impacts on Drug Development: A Narrative Review

Pharmaceuticals, Год журнала: 2023, Номер 16(11), С. 1615 - 1615

Опубликована: Ноя. 15, 2023

Antibiotics have revolutionized medicine, saving countless lives since their discovery in the early 20th century. However, origin of antibiotics is now overshadowed by alarming rise antibiotic resistance. This global crisis stems from relentless adaptability microorganisms, driven misuse and overuse antibiotics. article explores subsequent emergence It delves into mechanisms employed bacteria to develop resistance, highlighting dire consequences drug including compromised patient care, increased mortality rates, escalating healthcare costs. The elucidates latest strategies against drug-resistant encompassing innovative approaches such as phage therapy, CRISPR-Cas9 technology, exploration natural compounds. Moreover, it examines profound impact resistance on development, rendering pursuit new economically challenging. limitations challenges developing novel are discussed, along with hurdles regulatory process that hinder progress this critical field. Proposals for modifying facilitate development presented. withdrawal major pharmaceutical firms research examined, potential re-engage interest. also outlines initiatives overcome economic incentivize emphasizing international collaborations partnerships. Finally, sheds light government-led a specific focus Middle East. discusses proactive measures taken governments region, Saudi Arabia United Arab Emirates, combat threat. In face multifaceted approach imperative. provides valuable insights complex landscape challenges, collaborative efforts required ensure future where remain effective tools safeguarding public health.

Язык: Английский

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Mitochondrial dysfunction: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Май 15, 2024

Abstract Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation disease progression. Particularly, mitochondrial dysfunctions identified many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, cancer. However, the multifaceted nature elusive phenotypic threshold dysfunction complicate our understanding contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among most important therapeutic targets. In recent years, strategies targeting have continuously emerged transitioned clinical trials. Advanced intervention such as using healthy replenish or replace damaged mitochondria, has shown promise preclinical trials various Mitochondrial components, mtDNA, mitochondria-located microRNA, associated proteins can be potential agents augment function immunometabolic diseases tissue injuries. Here, we review current knowledge pathophysiology concrete examples We also summarize treat perspective dietary supplements targeted therapies, well translational situation related pharmacology agents. Finally, this discusses innovations applications transplantation an advanced promising treatment.

Язык: Английский

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Role of mitochondrial alterations in human cancer progression and cancer immunity

Journal of Biomedical Science, Год журнала: 2023, Номер 30(1)

Опубликована: Июль 31, 2023

Abstract Dysregulating cellular metabolism is one of the emerging cancer hallmarks. Mitochondria are essential organelles responsible for numerous physiologic processes, such as energy production, metabolism, apoptosis, and calcium redox homeostasis. Although “Warburg effect,” in which cells prefer aerobic glycolysis even under normal oxygen circumstances, was proposed a century ago, how mitochondrial dysfunction contributes to progression still unclear. This review discusses recent progress alterations DNA (mtDNA) dynamics malignant progression. Moreover, we integrate possible regulatory mechanism dysfunction–mediated retrograde signaling pathways, including mitochondrion-derived molecules (reactive species, calcium, oncometabolites, mtDNA) stress response pathways (mitochondrial unfolded protein integrated response) provide therapeutic targets. Furthermore, discuss findings on role mitochondria immune function reveal impact tumor microenvironment remodeling immunity. Targeting might improve immunotherapy. These suggest that targeting malignancy modulating immunity be promising treatment strategies patients precise personalized medicine against cancer.

Язык: Английский

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Mitochondrial stress and mitokines in aging

Aging Cell, Год журнала: 2023, Номер 22(2)

Опубликована: Янв. 15, 2023

Abstract Mitokines are signaling molecules that enable communication of local mitochondrial stress to other mitochondria in distant cells and tissues. Among those FGF21, GDF15 (both expressed the nucleus) several mitochondrial‐derived peptides, including humanin. Their responsiveness induces mitokine‐signaling response for example exercise, following challenges skeletal muscle. Such is emerging as an important mediator exercise‐derived dietary strategy‐related molecular systemic health benefits, healthy aging. A compensatory increase mitokine synthesis secretion could preserve function overall cellular vitality. Conversely, resistance against actions may also develop. Alterations mitokine‐levels, therefore mitokine‐related inter‐tissue cross talk, associated with general aging processes influence development age‐related chronic metabolic, cardiovascular neurological diseases; whether these changes contribute or represent “rescue factors” remains be conclusively shown. The aim present review summarize expanding knowledge on mitokines, potential modulate them by lifestyle their involvement diseases. We highlight importance well‐balanced preventive therapeutic properties maintaining homeostasis sensitivity but risks arising from dysregulation mitokines. While reduced levels impair inter‐organ crosstalk, excessive concentrations can have deleterious consequences conditions such cancer heart failure. Preservation achieved regular exercise increased lifespan.

Язык: Английский

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The multiple links between actin and mitochondria

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 24(9), С. 651 - 667

Опубликована: Июнь 5, 2023

Язык: Английский

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A break in mitochondrial endosymbiosis as a basis for inflammatory diseases

Nature, Год журнала: 2024, Номер 626(7998), С. 271 - 279

Опубликована: Фев. 7, 2024

Язык: Английский

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Ectotherm mitochondrial economy and responses to global warming

Acta Physiologica, Год журнала: 2023, Номер 237(4)

Опубликована: Фев. 15, 2023

Abstract Temperature is a key abiotic factor affecting ecology, biogeography, and evolution of species. Alterations energy metabolism play an important role in adaptations plastic responses to temperature shifts on different time scales. Mitochondrial affects cellular bioenergetics redox balance making these organelles determinant organismal performances such as growth, locomotion, or development. Here I analyze the impacts environmental mitochondrial functions (including oxidative phosphorylation, proton leak, production reactive oxygen species(ROS), ATP synthesis) ectotherms discuss mechanisms underlying negative economy caused by supraoptimal temperatures. Owing differences thermal sensitivity processes, elevated temperatures (beyond species‐ population‐specific optimal range) cause reallocation electron flux protonmotive force (Δp) way that decreases synthesis efficiency, elevates relative cost maintenance, causes excessive ROS raises for antioxidant defense. These might have consequences fitness traits tolerance growth. Correlation between indices mitochondria whole organism indicate experience similar selective pressures but further investigations are needed establish whether there cause‐effect relationship failure loss performance during change.

Язык: Английский

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Mitochondrial Transplantation in Mitochondrial Medicine: Current Challenges and Future Perspectives

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 1969 - 1969

Опубликована: Янв. 19, 2023

Mitochondrial diseases (MDs) are inherited genetic conditions characterized by pathogenic mutations in nuclear DNA (nDNA) or mitochondrial (mtDNA). Current therapies still far from being fully effective and covering the broad spectrum of mtDNA. For example, unlike heteroplasmic conditions, MDs caused homoplasmic mtDNA do not yet benefit advances molecular approaches. An attractive method providing dysfunctional cells and/or tissues with healthy mitochondria is transplantation. In this review, we discuss what known about intercellular transfer methods used to both vitro vivo, provide an outlook on future therapeutic applications. Overall, containing wild-type copies could induce a shift even when variants present, aim attenuating preventing progression pathological clinical phenotypes. summary, transplantation challenging but potentially ground-breaking option for treatment various pathologies, although several questions remain be addressed before its application medicine.

Язык: Английский

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Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

Advanced Materials, Год журнала: 2024, Номер 36(18)

Опубликована: Янв. 15, 2024

Abstract Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad vital functions across diverse cellular processes. Dysfunctions within mitochondria serve catalysts for various diseases, prompting widespread demise. Mounting research on remedying damaged indicates that constitute valuable target therapeutic intervention against diseases. But less clinical practice and lower recovery rate imply limitation traditional drugs, which need further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution high efficacy by capitalizing excellent nanomaterials targeting drug delivery. Mitochondria‐remedying nanodrugs achieved ideal effects. This review elucidates significance in cells organs, while also compiling mortality data related Correspondingly, nanodrug‐mediate strategies applicable mitochondria‐remedying disease are detailed, with full understanding roles dysfunction advantages nanodrugs. In addition, future challenges directions discussed. conclusion, this provides comprehensive insights into design development nanodrugs, aiming to help scientists who desire extend their fields engage interdisciplinary subject.

Язык: Английский

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