scholarly journals Mitochondrial Dysfunction in Cancer Cachexia: Impact on Muscle Health and Regeneration

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3150
Author(s):  
Marc Beltrà ◽  
Fabrizio Pin ◽  
Riccardo Ballarò ◽  
Paola Costelli ◽  
Fabio Penna
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Cancer Cachexia ◽  
Compensatory Mechanism ◽  
Mitochondrial Alterations ◽  
The One ◽  
Energy Failure

Cancer cachexia is a frequently neglected debilitating syndrome that, beyond representing a primary cause of death and cancer therapy failure, negatively impacts on patients’ quality of life. Given the complexity of its multisystemic pathogenesis, affecting several organs beyond the skeletal muscle, defining an effective therapeutic approach has failed so far. Revamped attention of the scientific community working on cancer cachexia has focused on mitochondrial alterations occurring in the skeletal muscle as potential triggers of the complex metabolic derangements, eventually leading to hypercatabolism and tissue wasting. Mitochondrial dysfunction may be simplistically viewed as a cause of energy failure, thus inducing protein catabolism as a compensatory mechanism; however, other peculiar cachexia features may depend on mitochondria. On the one side, chemotherapy also impacts on muscle mitochondrial function while, on the other side, muscle-impaired regeneration may result from insufficient energy production from damaged mitochondria. Boosting mitochondrial function could thus improve the energetic status and chemotherapy tolerance, and relieve the myogenic process in cancer cachexia. In the present work, a focused review of the available literature on mitochondrial dysfunction in cancer cachexia is presented along with preliminary data dissecting the potential role of stimulating mitochondrial biogenesis via PGC-1α overexpression in distinct aspects of cancer-induced muscle wasting.

Mitochondrial Metabolism in Cancer Cachexia: Novel Drug Target

2020 ◽  
Vol 20 (14) ◽  
pp. 1141-1153 ◽  
Author(s):  
Dhwani T. Dave ◽  
Bhoomika M. Patel
Keyword(s):  
Skeletal Muscle ◽  
Drug Target ◽  
Cancer Cachexia ◽  
Oxidative Capacity ◽  
Skeletal Muscle Wasting ◽  
Mitochondrial Alterations ◽  
Pertinent Information ◽  
Novel Drug

Background: Cancer cachexia is a metabolic syndrome prevalent in the majority of the advanced cancers and is associated with complications such as anorexia, early satiety, weakness, anaemia, and edema, thereby reducing performance and impairing quality of life. Skeletal muscle wasting is a characteristic feature of cancer-cachexia and mitochondria is responsible for regulating total protein turnover in skeletal muscle tissue. Methods: We carried out exhaustive search for cancer cachexia and role of mitochondria in the same in various databases. All the relevant articles were gathered and the pertinent information was extracted out and compiled which was further structured into different sub-sections. Results: Various findings on the mitochondrial alterations in connection to its disturbed normal physiology in various models of cancer-cachexia have been recently reported, suggesting a significant role of the organelle in the pathogenesis of the complications involved in the disorder. It has also been reported that reduced mitochondrial oxidative capacity is due to reduced mitochondrial biogenesis as well as altered balance between fusion and fission protein activities. Moreover, autophagy in mitochondria (termed as mitophagy) is reported to play an important role in cancer cachexia. Conclusions: The present review aims to put forth the changes occurring in mitochondria and hence explore possible targets which can be exploited in cancer-induced cachexia for treatment of such a debilitating condition.

scholarly journals MicroRNAs in Skeletal Muscle and Hints on Their Potential Role in Muscle Wasting During Cancer Cachexia

2020 ◽  
Vol 10 ◽  
Author(s):  
Gioacchino P. Marceca ◽  
Giovanni Nigita ◽  
Federica Calore ◽  
Carlo M. Croce
Keyword(s):  
Skeletal Muscle ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Phenotypic Alteration ◽  
Specific Tumor ◽  
Non Coding Rnas

Cancer-associated cachexia is a heterogeneous, multifactorial syndrome characterized by systemic inflammation, unintentional weight loss, and profound alteration in body composition. The main feature of cancer cachexia is represented by the loss of skeletal muscle tissue, which may or may not be accompanied by significant adipose tissue wasting. Such phenotypic alteration occurs as the result of concomitant increased myofibril breakdown and reduced muscle protein synthesis, actively contributing to fatigue, worsening of quality of life, and refractoriness to chemotherapy. According to the classical view, this condition is primarily triggered by interactions between specific tumor-induced pro-inflammatory cytokines and their cognate receptors expressed on the myocyte membrane. This causes a shift in gene expression of muscle cells, eventually leading to a pronounced catabolic condition and cell death. More recent studies, however, have shown the involvement of regulatory non-coding RNAs in the outbreak of cancer cachexia. In particular, the role exerted by microRNAs is being widely addressed, and several mechanistic studies are in progress. In this review, we discuss the most recent findings concerning the role of microRNAs in triggering or exacerbating muscle wasting in cancer cachexia, while mentioning about possible roles played by long non-coding RNAs and ADAR-mediated miRNA modifications.

scholarly journals Skeletal muscle insulin resistance: role of mitochondria and other ROS sources

2017 ◽  
Vol 233 (1) ◽  
pp. R15-R42 ◽  
Author(s):  
Sergio Di Meo ◽  
Susanna Iossa ◽  
Paola Venditti
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Early Event ◽  
Ros Production ◽  
Obese People ◽  
Skeletal Muscle Insulin Resistance ◽  
Mitochondrial Alterations

At present, obesity is one of the most important public health problems in the world because it causes several diseases and reduces life expectancy. Although it is well known that insulin resistance plays a pivotal role in the development of type 2 diabetes mellitus (the more frequent disease in obese people) the link between obesity and insulin resistance is yet a matter of debate. One of the most deleterious effects of obesity is the deposition of lipids in non-adipose tissues when the capacity of adipose tissue is overwhelmed. During the last decade, reduced mitochondrial function has been considered as an important contributor to ‘toxic’ lipid metabolite accumulation and consequent insulin resistance. More recent reports suggest that mitochondrial dysfunction is not an early event in the development of insulin resistance, but rather a complication of the hyperlipidemia-induced reactive oxygen species (ROS) production in skeletal muscle, which might promote mitochondrial alterations, lipid accumulation and inhibition of insulin action. Here, we review the literature dealing with the mitochondria-centered mechanisms proposed to explain the onset of obesity-linked IR in skeletal muscle. We conclude that the different pathways leading to insulin resistance may act synergistically because ROS production by mitochondria and other sources can result in mitochondrial dysfunction, which in turn can further increase ROS production leading to the establishment of a harmful positive feedback loop.

scholarly journals Early or advanced stage type 2 diabetes is not accompanied by in vivo skeletal muscle mitochondrial dysfunction

2008 ◽  
Vol 158 (5) ◽  
pp. 643-653 ◽  
Author(s):  
H M De Feyter ◽  
N M A van den Broek ◽  
S F E Praet ◽  
K Nicolay ◽  
L J C van Loon ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Resonance Spectroscopy ◽  
Diabetes Patients

ObjectiveSeveral lines of evidence support a potential role of skeletal muscle mitochondrial dysfunction in the pathogenesis of insulin resistance and/or type 2 diabetes. However, it remains to be established whether mitochondrial dysfunction represents either cause or consequence of the disease. We examined in vivo skeletal muscle mitochondrial function in early and advanced stages of type 2 diabetes, with the aim to gain insight in the proposed role of mitochondrial dysfunction in the aetiology of insulin resistance and/or type 2 diabetes.MethodsTen long-standing, insulin-treated type 2 diabetes patients, 11 subjects with impaired fasting glucose, impaired glucose tolerance and/or recently diagnosed type 2 diabetes, and 12 healthy, normoglycaemic controls, matched for age and body composition and with low habitual physical activity levels were studied. In vivo mitochondrial function of the vastus lateralis muscle was evaluated from post-exercise phosphocreatine (PCr) recovery kinetics using 31P magnetic resonance spectroscopy (MRS). Intramyocellular lipid (IMCL) content was assessed in the same muscle using single-voxel 1H MRS.ResultsIMCL content tended to be higher in the type 2 diabetes patients when compared with normoglycaemic controls (P=0.06). The31P MRS parameters for mitochondrial function, i.e. PCr and ADP recovery time constants and maximum aerobic capacity, did not differ between groups.ConclusionsThe finding that in vivo skeletal muscle oxidative capacity does not differ between long-standing, insulin-treated type 2 diabetes patients, subjects with early stage type 2 diabetes and sedentary, normoglycaemic controls suggests that mitochondrial dysfunction does not necessarily represent either cause or consequence of insulin resistance and/or type 2 diabetes.

Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients

2016 ◽  
Vol 22 (18) ◽  
pp. 2650-2656 ◽  
Author(s):  
Noelia Diaz-Morales ◽  
Susana Rovira-Llopis ◽  
Irene Escribano-Lopez ◽  
Celia Bañuls ◽  
Sandra Lopez-Domenech ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

scholarly journals Quality of learners at the start of each educational process

2019 ◽  
Vol 9 (14) ◽  
Author(s):  
Abdennasser Naji
Keyword(s):  
Control Systems ◽  
Preventive Measures ◽  
Educational Process ◽  
Service Needs ◽  
True Value ◽  
Previous Cycle ◽  
Set Up ◽  
The One

The education system is organized in the form of cycles, each feeding the one following it with learners. They will continue their studies in the destination cycle, and their future will certainly depend, at least in part, on the quality of the skills acquired in the previous cycle. Given the divergences and disparities existing between the different cycles mainly due to the fact that each responds to its own design logic and in the absence of coordination between them, there is a huge lack of quality to gain at the interface of the cycles . The referral system that plays the role of supply service needs to be updated to strengthen educational quality, but it is not the only one. It is also necessary to help the orienting staff to assess the quality of the learners at its true value, to set up partnership links between the cycles to help each other in favor of quality, and to set up reception control systems at the entry of each cycle, supported by corrective and preventive measures.

scholarly journals The vitamin D receptor regulates mitochondrial function in C2C12 myoblasts

2020 ◽  
Vol 318 (3) ◽  
pp. C536-C541 ◽  
Author(s):  
Stephen P. Ashcroft ◽  
Joseph J. Bass ◽  
Abid A. Kazi ◽  
Philip J. Atherton ◽  
Andrew Philp
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Protein Content ◽  
Vitamin D Receptor ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Oxidative Capacity ◽  
C2c12 Myoblasts

Vitamin D deficiency has been linked to a reduction in skeletal muscle function and oxidative capacity; however, the mechanistic bases of these impairments are poorly understood. The biological actions of vitamin D are carried out via the binding of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) to the vitamin D receptor (VDR). Recent evidence has linked 1α,25(OH)2D3 to the regulation of skeletal muscle mitochondrial function in vitro; however, little is known with regard to the role of the VDR in this process. To examine the regulatory role of the VDR in skeletal muscle mitochondrial function, we used lentivirus-mediated shRNA silencing of the VDR in C2C12 myoblasts (VDR-KD) and examined mitochondrial respiration and protein content compared with an shRNA scrambled control. VDR protein content was reduced by ~95% in myoblasts and myotubes ( P < 0.001). VDR-KD myoblasts displayed a 30%, 30%, and 36% reduction in basal, coupled, and maximal respiration, respectively ( P < 0.05). This phenotype was maintained in VDR-KD myotubes, displaying a 34%, 33%, and 48% reduction in basal, coupled, and maximal respiration ( P < 0.05). Furthermore, ATP production derived from oxidative phosphorylation (ATPOx) was reduced by 20%, suggesting intrinsic impairments within the mitochondria following VDR-KD. However, despite the observed functional decrements, mitochondrial protein content, as well as markers of mitochondrial fission were unchanged. In summary, we highlight a direct role for the VDR in regulating skeletal muscle mitochondrial respiration in vitro, providing a potential mechanism as to how vitamin D deficiency might impact upon skeletal muscle oxidative capacity.

scholarly journals MicroRNA-709 Mediates Acute Tubular Injury through Effects on Mitochondrial Function

2017 ◽  
Vol 29 (2) ◽  
pp. 449-461 ◽  
Author(s):  
Yan Guo ◽  
Jiajia Ni ◽  
Shuang Chen ◽  
Mi Bai ◽  
Jiajuan Lin ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Cell Injury ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Tubular Injury ◽  
Pathogenic Role ◽  
Novel Target

Mitochondrial dysfunction has important roles in the pathogenesis of AKI, yet therapeutic approaches to improve mitochondrial function remain limited. In this study, we investigated the pathogenic role of microRNA-709 (miR-709) in mediating mitochondrial impairment and tubular cell death in AKI. In a cisplatin-induced AKI mouse model and in biopsy samples of human AKI kidney tissue, miR-709 was significantly upregulated in the proximal tubular cells (PTCs). The expression of miR-709 in the renal PTCs of patients with AKI correlated with the severity of kidney injury. In cultured mouse PTCs, overexpression of miR-709 markedly induced mitochondrial dysfunction and cell apoptosis, and inhibition of miR-709 ameliorated cisplatin-induced mitochondrial dysfunction and cell injury. Further analyses showed that mitochondrial transcriptional factor A (TFAM) is a target gene of miR-709, and genetic restoration of TFAM attenuated mitochondrial dysfunction and cell injury induced by cisplatin or miR-709 overexpression in vitro. Moreover, antagonizing miR-709 with an miR-709 antagomir dramatically attenuated cisplatin-induced kidney injury and mitochondrial dysfunction in mice. Collectively, our results suggest that miR-709 has an important role in mediating cisplatin-induced AKI via negative regulation of TFAM and subsequent mitochondrial dysfunction. These findings reveal a pathogenic role of miR-709 in acute tubular injury and suggest a novel target for the treatment of AKI.

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