AMPK is mitochondrial medicine for neuromuscular disorders

Mikhail, Andrew; Ng, Sean Y.; Mattina, Stephanie R; Ljubicic, Vladimir

doi:10.1016/j.molmed.2023.03.008

Cited by 9 publications

(5 citation statements)

References 102 publications

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“…Another explanation for the increase in FNM oocytes’ MMP may be that mitochondrial fusion during IVM is increased by FLI supplementation. Specifically, IGF1 has been shown to activate AMP-activated protein kinase (AMPK), and upregulation of AMPK increases mitochondrial fusion [ 39 , 40 ]. Mitochondrial fusion is necessary for proper mitochondrial function under stress conditions, which are present during IVM of oocytes [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Cytokine-Supplemented Maturation Medium Enhances Cytoplasmic and Nuclear Maturation in Bovine Oocytes

Blocher,

Liu,

Patrick

et al. 2024

Animals

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Bovine in vitro oocyte maturation (IVM) is an easy way to obtain oocytes for subsequent assisted reproductive techniques but is inefficient compared to in vivo maturation. Supplementation of three cytokines, fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF), and insulin-like growth factor 1 (IGF1), or FLI, has increased oocyte maturation and embryo development in multiple species, but studies have not explored the oocyte differences caused by FLI IVM supplementation. This study aimed to assess important nuclear and cytoplasmic maturation events in high-quality oocytes. FLI-supplemented oocytes had a decreased GV (3.0% vs. 13.7%, p < 0.01) and increased telophase I incidence (34.6% vs. 17.6%, p < 0.05) after IVM, increased normal meiotic spindles (68.8% vs. 50.0%, p < 0.001), and an increased nuclear maturation rate (75.1% vs. 66.8%, p < 0.001). Moreover, in metaphase II oocytes, the percentage of FLI-treated oocytes with a diffuse mitochondrial distribution was higher (87.7% vs. 77.5%, p < 0.05) and with a cortical mitochondrial distribution was lower (11.6% vs. 17.4%, p < 0.05). Additionally, FLI-supplemented oocytes had more pattern I cortical granules (21.3% vs. 14.4%, p < 0.05). These data suggest that FLI supplementation in bovine in vitro maturation medium coordinates nuclear and cytoplasmic maturation to produce higher-quality oocytes.

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Section: Discussionmentioning

confidence: 99%

Cytokine-Supplemented Maturation Medium Enhances Cytoplasmic and Nuclear Maturation in Bovine Oocytes

Blocher,

Liu,

Patrick

et al. 2024

Animals

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“…Specifically, ATP is a sensitive signal of mitochondrial health, and a continuous decrease in intracellular ATP levels increases the relative AMP content and activates the AMP-protein kinase signalling pathway [122]. The activated 5'-AMPactivated protein kinase (AMPK) signalling pathway further regulates key enzymes in other metabolic pathways (including fat and glucose metabolism, mitochondrial dynamics, autophagy, and protein synthesis) through phosphorylation and indirectly restores the energy balance in the mitochondria [123,124]. Disruption of this mechanism results in various mitochondria-related diseases.…”

Section: Mitochondrial Dysregulation By Pleiotropic Stress Pathwaysmentioning

confidence: 99%

Molecular mechanisms of aging and anti-aging strategies

Li,

Tian,

Luo

et al. 2024

Cell Commun Signal

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Aging is a complex and multifaceted process involving a variety of interrelated molecular mechanisms and cellular systems. Phenotypically, the biological aging process is accompanied by a gradual loss of cellular function and the systemic deterioration of multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that aging is closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, loss of nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, loss of protein balance, deregulated nutrient sensing, altered intercellular communication, and dysbiosis. These age-related changes may be alleviated by intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, and targeted longevity genes. In this review, we summarise the key historical progress in the exploration of important causes of aging and anti-aging strategies in recent decades, which provides a basis for further understanding of the reversibility of aging phenotypes, the application prospect of synthetic biotechnology in anti-aging therapy is also prospected.

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“…Alternative non-pharmacological therapeutic strategies to improve mitochondrial health and biogenesis. Besides pharmacological/genetic interventions, exercise training, a non-pharmacological tool, has been extensively studied as an effective treatment in several neuromuscular disorders to promote mitochondrial biogenesis and preserve metabolic homeostasis (Mikhail et al, 2023;Trefts & Shaw, 2021). In healthy populations, endurance and resistance exercises have been known to provide a potent stimulus to elicit robust mitochondrial and hypertrophic adaptations to enhance muscle strength/power, mitochondrial oxidative capacity and cardiovascular fitness.…”

Section: Strategies Targeting Processes Related To Mitochondrial Ca 2+mentioning

confidence: 99%

“…Mitochondrial dysfunction is not unique to ALS but is commonly observed in other neuromuscular disorders including Duchenne muscular dystrophy, myotonic dystrophy, spinal muscular atrophy and Charcot-Marie-Tooth disease type 2A (Cantó-Santos et al, 2020;Mikhail et al, 2023), all of which could benefit from exercise training to activate AMPK and PGC1α pathways and improve mitochondrial health. Exercise training has been used in ALS patients to improve MN and muscle function with promising results (Bello-Haas et al, 2007;Desseille et al, 2017;Gillon et al, 2018;Jensen et al, 2017;Lunetta et al, 2016;Merico et al, 2018;Tsitkanou J Physiol 602.8 et al, 2019).…”

Section: Strategies Targeting Processes Related To Mitochondrial Ca 2+mentioning

confidence: 99%

Targeting mitochondrial Ca²⁺ uptake for the treatment of amyotrophic lateral sclerosis

Zhong,

Rua,

Wei‐LaPierre

2023

The Journal of Physiology

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Amyotrophic lateral sclerosis (ALS) is a rare adult‐onset neurodegenerative disease characterized by progressive motor neuron (MN) loss, muscle denervation and paralysis. Over the past several decades, researchers have made tremendous efforts to understand the pathogenic mechanisms underpinning ALS, with much yet to be resolved. ALS is described as a non‐cell autonomous condition with pathology detected in both MNs and non‐neuronal cells, such as glial cells and skeletal muscle. Studies in ALS patient and animal models reveal ubiquitous abnormalities in mitochondrial structure and function, and disturbance of intracellular calcium homeostasis in various tissue types, suggesting a pivotal role of aberrant mitochondrial calcium uptake and dysfunctional calcium signalling cascades in ALS pathogenesis. Calcium signalling and mitochondrial dysfunction are intricately related to the manifestation of cell death contributing to MN loss and skeletal muscle dysfunction. In this review, we discuss the potential contribution of intracellular calcium signalling, particularly mitochondrial calcium uptake, in ALS pathogenesis. Functional consequences of excessive mitochondrial calcium uptake and possible therapeutic strategies targeting mitochondrial calcium uptake or the mitochondrial calcium uniporter, the main channel mediating mitochondrial calcium influx, are also discussed. image

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AMPK is mitochondrial medicine for neuromuscular disorders

Cited by 9 publications

References 102 publications

Cytokine-Supplemented Maturation Medium Enhances Cytoplasmic and Nuclear Maturation in Bovine Oocytes

Cytokine-Supplemented Maturation Medium Enhances Cytoplasmic and Nuclear Maturation in Bovine Oocytes

Molecular mechanisms of aging and anti-aging strategies

Targeting mitochondrial Ca²⁺ uptake for the treatment of amyotrophic lateral sclerosis

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AMPK is mitochondrial medicine for neuromuscular disorders

Cited by 9 publications

References 102 publications

Cytokine-Supplemented Maturation Medium Enhances Cytoplasmic and Nuclear Maturation in Bovine Oocytes

Cytokine-Supplemented Maturation Medium Enhances Cytoplasmic and Nuclear Maturation in Bovine Oocytes

Molecular mechanisms of aging and anti-aging strategies

Targeting mitochondrial Ca2+ uptake for the treatment of amyotrophic lateral sclerosis

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Product

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About

Targeting mitochondrial Ca²⁺ uptake for the treatment of amyotrophic lateral sclerosis