Direct Cell-Cell Communication via Membrane Pores, Gap Junction Channels, and Tunneling Nanotubes: Medical Relevance of Mitochondrial Exchange DOI Open Access
Eliseo A. Eugenín, Enrico M. Camporesi, Camillo Peracchia

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 6133 - 6133

Published: May 30, 2022

The history of direct cell-cell communication has evolved in several small steps. First discovered the 1930s invertebrate nervous systems, it was thought at first to be an exception "cell theory", restricted invertebrates. Surprisingly, however, 1950s, electrical also reported vertebrates. Once more, excitable cells. In contrast, mid-1960s, two startling publications proved that virtually all cells freely exchange neutral and charged molecules. Soon after, by gap junction channels reported. While junctions are major means communication, early 1980s, evidence surfaced some might communicate via membrane pores. Questions were raised about possible artifactual nature However, this century, we learned pores exists plays a role medicine, as structures involved, "tunneling nanotubes", can rescue diseased directly transferring healthy mitochondria into compromised tissues. On other hand, pathogens/cancer could use these systems amplify pathogenesis. Here, describe evolution discovery new potential therapeutic impact on uncurable diseases.

Language: Английский

The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies DOI Open Access
Celia Andrés, José Manuel Pérez de la Lastra, Francisco J. Plou

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(9), P. 4642 - 4642

Published: April 28, 2021

Living species are continuously subjected to all extrinsic forms of reactive oxidants and others that produced endogenously. There is extensive literature on the generation effects oxygen (ROS) in biological processes, both terms alteration their role cellular signaling regulatory pathways. Cells produce ROS as a controlled physiological process, but increasing becomes pathological leads oxidative stress disease. The induction an imbalance between production radical antioxidant defense systems, which can cause damage biomolecules, including lipids, proteins DNA. Cellular biochemical experiments have been complemented various ways explain chemistry oxidants. However, it often unclear how this translates into chemical reactions involving redox changes. This review addresses question includes robust mechanistic explanation stress.

Language: Английский

Citations

1580
Metformin: Is it a drug for all reasons and diseases? DOI Creative Commons
Chris R. Triggle, Ibrahim Mohammed, Khalifa Bshesh

et al.

Metabolism, Journal Year: 2022, Volume and Issue: 133, P. 155223 - 155223

Published: May 29, 2022

Metformin was first used to treat type 2 diabetes in the late 1950s and 2022 remains first-choice drug daily by approximately 150 million people. An accumulation of positive pre-clinical clinical data has stimulated interest re-purposing metformin a variety diseases including COVID-19. In polycystic ovary syndrome improves insulin sensitivity. 1 may help reduce dose. Meta-analysis from studies link reduction incidence cancer. Clinical trials, MILES (Metformin Longevity Study), TAME (Targeting Aging with Metformin), have been designed determine if can offset aging extend lifespan. Pre-clinical suggest that metformin, via suppression pro-inflammatory pathways, protection mitochondria vascular function, direct actions on neuronal stem cells, protect against neurodegenerative diseases. also studied for its anti-bacterial, -viral, -malaria efficacy. Collectively, these raise question: Is all diseases? It unclear as whether putative beneficial effects are secondary an anti-hyperglycemic insulin-sensitizing drug, or result other cellular actions, inhibition mTOR (mammalian target rapamycin), anti-viral actions. Clarification is sought ex vivo based use high concentrations be translated into benefits, they reflect 'Paracelsus' effect. The environmental impact no known metabolites, another emerging issue linked endocrine disruption fish, extensive T2D raised concerns over human reproduction. objectives this review to: 1) evaluate mechanism(s) action metformin; 2) analyze controversial evidence metformin's effectiveness treatment than diabetes; 3) assess reproducibility data, finally 4) reach informed conclusion reasons. We conclude primary benefits antihyperglycaemic secondarily contribute reduced risk number thereby enhancing healthspan. However, like improving endothelial function independent glucose homeostasis add therapeutic

Language: Английский

Citations

182
Mitochondria: It is all about energy DOI Creative Commons

Amaloha Casanova,

Anne Wevers, Santiago Navarro‐Ledesma

et al.

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: April 25, 2023

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron calcium homeostasis the of hormones neurotransmitters, such as melatonin. They enable influence communication at all physical levels through interaction with other organelles, nucleus, outside environment. The literature suggests crosstalk between mitochondria circadian clocks, gut microbiota, immune system. might even be hub supporting integrating activity across these domains. Hence, they (missing) link Mitochondrial dysfunction related metabolic syndrome, neuronal diseases, cancer, cardiovascular infectious inflammatory disorders. In this regard, diseases Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), pain are discussed. This review focuses on understanding mitochondrial action that allow for maintenance pathways toward dysregulated mechanisms. Although have allowed us adapt changes over course evolution, turn, evolution has shaped mitochondria. Each evolution-based intervention influences its own way. use physiological stress triggers tolerance stressor, achieving adaptability resistance. describes strategies could recover functioning providing comprehensive, root-cause-focused, integrative approach recovering treating people suffering diseases.

Language: Английский

Citations

95
Mitochondrial related genome-wide Mendelian randomization identifies putatively causal genes for multiple cancer types DOI Creative Commons
Yanni Li, Kristina Sundquist, Naiqi Zhang

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 88, P. 104432 - 104432

Published: Jan. 10, 2023

Language: Английский

Citations

43
SIRT1 activation attenuates palmitate induced apoptosis in C2C12 muscle cells DOI
Gholamreza Taheripak,

Niusha Sabeti,

Naba Najar

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Feb. 24, 2024

Language: Английский

Citations

19
Gut microbiota, nutrition, and mental health DOI Creative Commons
Gia Merlo, Gabrielle Bachtel, Steven G. Sugden

et al.

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 9, 2024

The human brain remains one of the greatest challenges for modern medicine, yet it is most integral and sometimes overlooked aspects medicine. consists roughly 100 billion neurons, trillion neuronal connections consumes about 20–25% body’s energy. Emerging evidence highlights that insufficient or inadequate nutrition linked to an increased risk health, mental psychological functioning compromise. A core component this relationship includes intricate dynamics brain-gut-microbiota (BGM) system, which a progressively recognized factor in sphere mental/brain health. bidirectional between brain, gut, gut microbiota along BGM system not only affects nutrient absorption utilization, but also exerts substantial influence on cognitive processes, mood regulation, neuroplasticity, other indices Neuroplasticity brain’s capacity adaptation neural regeneration response stimuli. Understanding neuroplasticity considering interventions enhance remarkable ability change through experience constitutes burgeoning area research has potential improving well-being, resilience, overall health optimal lifestyle interventions. nexus both academic clinical perspectives nutritional neuroscience emerges as potent tool patient outcomes, proactively mitigate challenges, improve management treatment existing conditions by championing health-promoting dietary patterns, rectifying deficiencies, seamlessly integrating nutrition-centered strategies into care.

Language: Английский

Citations

17
Inter and Intracellular mitochondrial trafficking in health and disease DOI
Santhanam Shanmughapriya, Dianne Langford, Kalimuthusamy Natarajaseenivasan

et al.

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 62, P. 101128 - 101128

Published: July 23, 2020

Language: Английский

Citations

107
Novel approach to quantify mitochondrial content and intrinsic bioenergetic efficiency across organs DOI Creative Commons
Kelsey McLaughlin, James T. Hagen,

Hannah S. Coalson

et al.

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: Oct. 19, 2020

Abstract Human disease pathophysiology commonly involves metabolic disruption at both the cellular and subcellular levels. Isolated mitochondria are a powerful model for separating global changes from intrinsic mitochondrial alterations. However, common laboratory practices isolating (e.g., differential centrifugation) routinely results in organelle preparations with variable purity. To overcome this issue, we developed mass spectrometry-based method that quantitatively evaluates sample-specific percent enrichment. Sample-specific enrichment was then used to correct various biochemical readouts of function ‘fixed’ amount protein, thus allowing bioenergetics, relative underlying proteome, be assessed across multiple mouse tissues heart, brown adipose, kidney, liver). Our support use mitochondrial-targeted nLC-MS/MS as quantitate on per-sample basis, unbiased comparison functional parameters between populations isolated metabolically distinct tissues. This can easily applied experimental settings which shifts network suspected driving given physiological or pathophysiological outcome.

Language: Английский

Citations

103
Mitochondrial contributions to vascular endothelial dysfunction, arterial stiffness, and cardiovascular diseases DOI
Danielle L. Kirkman, Austin T. Robinson, Matthew J. Rossman

et al.

AJP Heart and Circulatory Physiology, Journal Year: 2021, Volume and Issue: 320(5), P. H2080 - H2100

Published: April 9, 2021

Cardiovascular disease (CVD) affects one in three adults and remains the leading cause of death America. Advancing age is a major risk factor for CVD. Recent plateaus CVD-related mortality rates high-income countries after decades decline highlight critical need to identify novel therapeutic targets strategies mitigate manage CVD development progression. Vascular dysfunction, characterized by endothelial dysfunction large elastic artery stiffening, independently associated with an increased incidence therefore attractive target prevention management. mitochondria have emerged as important player maintaining vascular homeostasis. As such, age- disease-related impairments mitochondrial function contribute consequent increases risk. This review outlines role discusses ramifications on health setting disease. The adverse consequences mitochondrial-derived reactive oxygen species, impaired quality control, defective calcium cycling are emphasized, particular. Current evidence both lifestyle pharmaceutical mitochondrial-targeted improve also presented.

Language: Английский

Citations

86
The Role of Mitochondria in Cardiovascular Diseases DOI Creative Commons
Anastasia V. Poznyak, Ekaterina A. Ivanova, Igor A. Sobenin

et al.

Biology, Journal Year: 2020, Volume and Issue: 9(6), P. 137 - 137

Published: June 25, 2020

The role of mitochondria in cardiovascular diseases is receiving ever growing attention. As a central player the regulation cellular metabolism and powerful controller fate, appear to comprise an interesting potential therapeutic target. With development DNA sequencing methods, mutations mitochondrial (mtDNA) became subject intensive study, since many directly lead dysfunction, oxidative stress, deficient energy production and, as result, cell dysfunction death. Many mtDNA were found be associated with chronic human diseases, including disorders. In particular, 17 reported ischemic heart disease humans. this review, we discuss involvement pathogenesis atherosclerosis describe identified so far that are its risk factors.

Language: Английский

Citations

84