Результаты поиска

A review of mitochondrial dysfunction in diabetic sarcopenia: Mechanisms, diagnosis, and treatment approaches.

Diabetic sarcopenia is a common complication of diabetes, substantially impacting patients' quality of life and prognosis. Its pathogenesis is closely related to energy metabolism, with mitochondria-often referred to as the cellular "powerhouse"-playing a central role in this process. This review focuses on the role of mitochondrial dysfunction in diabetic sarcopenia, emphasizing mechanisms such as energy metabolism imbalance, oxidative stress-induced damage, and abnormalities in mitochondrial biogenesis and dynamics. Additionally, we discussed current research on diagnostic and therapeutic st

Совпадение в полном тексте источника
… In terms of mitochondrial dynamics, the balance between fusion and fission is disrupted, leading to structural disorganization of the mitochondrial network. … At the molecular level, hyperglycemia disrupts mitochondrial dynamics by overactivating the fission protein Drp1 and suppressing the fusion protein Mfn2, driving mitochondrial fragmentation and metabolic collapse. …

Mitochondrial Genome Variants as a Cause of Mitochondrial Cardiomyopathy.

Mitochondria are small double-membraned organelles responsible for the generation of energy used in the body in the form of ATP. Mitochondri … ation of alternative metabolic pathways, the accumulation of reactive oxygen species, dysfunctional mitochondrial dynamics, abnormal calcium homeostasis, and mitochondrial iron overload. Here, we highlight the clinical assessment of mtDNA-related mitochondrial cardiomyopathy and offer a novel hypothesis of a possible integrated, multivariable pathophysiology of disease.

Linking Mitochondrial Gene Dysregulation to Immune Cell Shifts in Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a hereditary retinal disease characterized by the progressive degeneration of photoreceptor and retinal pigment epithelial (RPE) cells, ultimately leading to significant vision loss. While the pathogenesis of RP is associated with mitochondrial dysfunction and immune-inflammatory responses, the specific interplay between disrupted mitochondrial gene expression and immune cell infiltration remains inadequately understood. While gene therapy has been approved for a subset of RP patients with monogenic mutations such as RPE65-associated RP, it has notable limitations

Targeting mitochondria to protect the heart: a matter of balance?

Mitochondria are dynamic, undergoing both fission and fusion. Evidence indicates that a balance between these two processes is necessary to … study appearing in Clinical Science, Maneechote et al. assessed whether correcting the imbalance in mitochondrial dynamics with I/R by enhancing fusion would also be protective. Using a rat model, they investigated the efficacy of pharmacological intervention with mitochondrial fusion promoter-M1 (M1) given before ischemia, during ischemia, or at the onset of reperfusio …

Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.

Aging is a complex biological process characterized by the functional decline of multiple cellular organelles, with mitochondrial dysfunction emerging as a predominant hallmark. Alterations in mitochondria within senescent cells primarily encompass two interrelated aspects: intrinsic mitochondrial dysfunction and compromised mitochondrial quality control systems, including mitophagy, dynamics, and biogenesis. However, a comprehensive synthesis that bridges mechanistic insights into mitochondrial dysfunction with an analysis of therapeutic obstacles remains lacking. Here, we systematically summ

Bypassing mitochondrial defects rescues Huntington's phenotypes in Drosophila.

Huntington's disease (HD) is a fatal neurodegenerative disease with limited treatment options. Human and animal studies have suggested that … e defects. In particular, we find that co-expression of parkin, an E3 ubiquitin ligase critical for mitochondrial dynamics and homeostasis, produces significant enhancement of mitochondrial respiration when expressed either in neurons or muscles, resulting in significant rescue of neurodegeneration, viability and longevity in HD model flies. Targeting mutant HTT to musc …

Mitochondrial Quality Control via Mitochondrial Unfolded Protein Response (mtUPR) in Ageing and Neurodegenerative Diseases.

Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the ac…

Administration of Enalapril Started Late in Life Attenuates Hypertrophy and Oxidative Stress Burden, Increases Mitochondrial Mass, and Modulates Mitochondrial Quality Control Signaling in the Rat Heart.

Mitochondrial dysfunction is a relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at a non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the hearts of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n = 8) or placebo (n = 8) from 24 to 27 months of age. We also assessed mit

Impairing the mitochondrial fission and fusion balance: a new mechanism of neurodegeneration.

Mitochondrial dysfunction is a common characteristic of all neurodegenerative diseases. However, the cause of this dysfunction remains a mystery. Here, we discuss the potential role of mitochondrial fission and fusion in the onset and progression of neurodegenerative diseases. Specifically, we propose that an imbalance in mitochondrial fission and fusion may underlie both familial and sporadic neurodegenerative disorders. There is substantial evidence that links disruption of the mitochondrial fission and fusion equilibrium, resulting in abnormally long or short mitochondria, to neurodegenerat

Mitochondria in muscle stem cell biology: gatekeepers of fate, function, and regeneration.

Muscle stem cells (MuSCs) are essential for skeletal muscle regeneration and maintenance of tissue homeostasis. However, their regenerative capacity declines with aging and in several pathological conditions, including neuromuscular diseases, cancer cachexia, sepsis, and metabolic disorders. Increasing evidence has identified mitochondria as key regulators of MuSC behavior, influencing quiescence, activation, self-renewal, and differentiation during myogenesis. In addition to their role in energy production, mitochondria function as metabolic and signaling hubs that integrate cellular and envi

Homocysteine and Mitochondria in Cardiovascular and Cerebrovascular Systems.

Elevated concentration of homocysteine (Hcy) in the blood plasma, hyperhomocysteinemia (HHcy), has been implicated in various disorders, including cardiovascular and neurodegenerative diseases. Accumulating evidence indicates that pathophysiology of these diseases is linked with mitochondrial dysfunction. In this review, we discuss the current knowledge concerning the effects of HHcy on mitochondrial homeostasis, including energy metabolism, mitochondrial apoptotic pathway, and mitochondrial dynamics. The recent studies suggest that the interaction between Hcy and mitochondria is complex, and …

Loss of the mitochondrial i-AAA protease YME1L leads to ocular dysfunction and spinal axonopathy.

Disturbances in the morphology and function of mitochondria cause neurological diseases, which can affect the central and peripheral nervous system. The i-AAA protease YME1L ensures mitochondrial proteostasis and regulates mitochondrial dynamics by processing of the dynamin-like GTPase OPA1. Mutations in YME1L cause a multi-systemic mitochondriopathy associated with neurological dysfunction and mitochondrial fragmentation but pathogenic mechanisms remained enigmatic. Here, we report on striking cell-type-specific defects in mice lacking YME1L in the nervous system. YME1L-deficient mice manifes…

4-hydroxybenzoic acid induces browning of white adipose tissue through the AMPK-DRP1 pathway in HFD-induced obese mice.

BACKGROUND: Beige adipocytes have physiological functions similar to brown adipocytes, which are available to increase energy expenditure through uncoupling protein 1 (UCP1) within mitochondria. Recently, many studies showed white adipocytes can undergo remodeling into beige adipocytes, called "browning", by increasing fusion and fission events referred to as mitochondrial dynamics. PURPOSE: In this study, we aimed to investigate the browning effects of 4-hydroxybenzoic acid (4-HA), one of the major compounds of black raspberries. METHODS: We examined the mechanism underlying the browning pr…

Hydrogen sulfide alleviates hyperoxia effects on mitochondria in human developing airway smooth muscle.

Moderate hyperoxia (30%-60% O2) in premature infants promotes bronchial airway hyperresponsiveness (AHR) via airway smooth muscle (ASM), a key regulator of bronchoconstriction, bronchodilation, and remodeling. Understanding how O2 exposure drives long-term bronchial changes in prematurity is critical for developing therapies for airway disease across the lifespan. Premature lungs have immature antioxidant defenses, potentially due to disrupted mitochondrial dynamics, increasing susceptibility to O2-induced oxidative stress. Thus, mitochondrial homeostasis is highly relevant to ASM dysfunction …

Mitochondrial homeostasis collapse to cardiac remodeling: From mechanisms to novel targeted therapeutic avenues.

Myocardial remodeling is a common pathological process in various cardiovascular diseases (CVDs) and represents the heart's adaptive response to pressure or volume overload. However, prolonged myocardial remodeling often leads to a progressive decline in cardiac function, ultimately resulting in heart failure (HF). This process is primarily characterized by myocardial hypertrophy and fibrosis, both of which are closely linked to mitochondrial dysfunction. Emerging research uncovers a pivotal orchestrator of this lethal transition: mitochondrial homeostasis. As the powerhouse of cardiomyocytes,

Regulation of mitochondrial dysfunction induced cell apoptosis is a potential therapeutic strategy for herbal medicine to treat neurodegenerative diseases.

Neurodegenerative disease is a progressive neurodegeneration caused by genetic and environmental factors. Alzheimer's disease (AD), Parkinso … ses is closely related to the mitochondrial dysfunction, which can affect mitochondrial biogenesis, mitochondrial dynamics, as well as mitochondrial mitophagy. Through the disruption of mitochondrial homeostasis, nerve cells undergo varying degrees of apoptosis. Interestingly, it has been shown in recent years that the natural agents derived from herbal medicines are be …

Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed.

Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, … ion/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is …

Powerhouse failure and oxidative damage in autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disease due to mutations in SACS, which encodes sacsin, a protein localized on the mitochondrial surface and possibly involved in mitochondrial dynamics. In view of the possible mitochondrial involvement of sacsin, we investigated mitochondrial activity at functional and molecular level in skin fibroblasts obtained from ARSACS patients. We observed remarkable bioenergetic damage in ARSACS cells, as indicated by reduced basal, adenosine triphosphate (ATP)-linked and maximal mitochondrial respiration rate, …

Phylogeographic dynamics of the arthropod vector, the blacklegged tick (Ixodes scapularis).

BACKGROUND: The emergence of vector-borne pathogens in novel geographic areas is regulated by the migration of their arthropod vectors. Blacklegged ticks (Ixodes scapularis) and the pathogens they vector, including the causative agents of Lyme disease, babesiosis and anaplasmosis, continue to grow in their population sizes and to expand in geographic range. Migration of this vector over the previous decades has been implicated as the cause of the re-emergence of the most prevalent infectious diseases in North America. METHODS: We systematically collected ticks from across New York State (here

Mitochondrial Quality Control and Pathogenic Signaling Networks in Parkinson's Disease.

The second most prevalent neurodegenerative illness in the world, Parkinson's disease (PD), currently has no viable treatments. Although it is yet unknown if mitochondrial dysfunction is an initial event or evolves as a result of neurodegeneration, it is thought to be a crucial component of Parkinson's disease etiology. From the perspective of mitochondrial quality control (MQC), which includes PINK1/Parkin-mediated mitophagy, mitochondrial dynamics, and mitochondrial proteostasis, this article examines mitochondrial dysfunction. Together, these processes preserve mitochondrial homeostasis and…