scholarly journals Mitochondrial quality control in insulin resistance and diabetes

2016 ◽  
Vol 38 ◽  
pp. 118-126 ◽  
Author(s):  
Jonathan Wanagat ◽  
Andrea L Hevener
2019 ◽  
Vol 53 ◽  
pp. 166-175 ◽  
Author(s):  
Xiao Yu ◽  
Shasha Huang ◽  
Qianchun Deng ◽  
Yuhan Tang ◽  
Ping Yao ◽  
...  

2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Can Li ◽  
Nan Li ◽  
Yong Zhang

Objective To investigate how different skeletal muscle fiber types affect development of insulin resistance, and to explore the role of mitochondrial quality control system, especially mitochondrial unfolded protein response (UPRmt) and mitophagy, in response to metabolic stresses. Methods Male Wistar rats were randomly divided into 2 groups: fed with the normal diet for 8 weeks (Con), and fed with 45% high-fat diet for 8 weeks (IR). Fasting blood glucose (FBG), fasting insulin (FIN) and oral glucose tolerance test (OGTT) were used to identify insulin resistance model. Gastrocnemius (GC), soleus (SOL) and tibialis anterior (TA) muscle were isolated, and RT-qPCR was used to determine the expression of Myhc7, Myhc4. Oxygraph-2k was used to determine the mitochondrial State 3 (ST3), State 4(ST4) respiration and respiration control rate (RCR). JC-1 probe was used to measure mitochondrial membrane potential. Western Blot was used to determine the expressions of marker proteins of muscle fiber types (Myhc4, Myhc7), UPRmt related proteins (Hsp60, Hsp70) and mitophagy related proteins (Pink1, LC3). Results Compared with Con group, in IR group, FBG (7.1±1.27 vs. 5.4±0.43,p<0.05), FIN (19.4±5.2 vs. 31.6±6.7,p<0.05 ) and OGTT (area under the curve, about 31.7% increases, p<0.05) were significantly higher. Myhc4 mRNA (relative fold about 55.6% increases) and protein expression (about 33.9% increases, p<0.05) were significantly higher in GC. Myhc4 protein expression was significantly higher in GC (about 60.5% increases, p<0.05). While Myhc7 mRNA expression (about 51.1% decreases, p<0.05) was significantly lower in SOL. Compared with Con group, in IR group, mitochondrial RCR in SOL muscle was significantly lower (about 22.5% decreases, p<0.05). Furthermore, the expression of HSP60 (about 36.7% increases,p<0.05) and HSP70 (about 44.3% increases,p<0.05) was significantly higher in TA muscle, while the expression of Parkin (about 18.8% decreases,p<0.05) and the ratio between LC3 II/I (about 26.0% decreases,p<0.05)expression in SOL muscle were significantly lower. Conclusions In this study, we found that the percentage of fast muscle fibers was elevated in IR skeletal muscle, which were supported by increased Myhc4 and decreased Myhc7 level. Impaired mitochondrial function was only observed in slow muscle as inhibition of mitochondrial respiration. As marker of UPRmt, HSP60/70 were specifically activated in fast muscle in IR, while mitophagy-related proteins were specifically increased in slow muscle. These results indicate that mitochondrial quality control systems are selectively activated to recover mitochondrial functions depending on muscle fiber types in insulin resistant rat.


2020 ◽  
Vol 244 (2) ◽  
pp. 383-393 ◽  
Author(s):  
Baiyang You ◽  
Yaoshan Dun ◽  
Wenliang Zhang ◽  
Lingjun Jiang ◽  
Hui Li ◽  
...  

Mitochondrial quality control (MQC) and function are determinants for cellular energy metabolism, and their disorders are reported to play an important role in the development of insulin resistance (IR). Salidroside was reported to have beneficial effects on MQC through AMPK pathway; however, it is unknown whether salidroside exerts anti-IR effect with this action. This study sought to investigate the effects of salidroside on IR with an exploration of the mechanisms of its action. Experimental IR models were adopted in high-fat-diet (HFD)-fed mice and palmitate-treated C2C12 myotubes, respectively. Blood levels of glucose and insulin as well as cellular glucose uptake were determined, and mitochondrial function and MQC-associated parameters and reactive oxygen species (ROS) production were analyzed based on treatments with the activator (AICAR), inhibitors (compound C and EX-527) or specific siRNA of Ampk/Sirt1 and mitochondrial ROS scavenger (mito-TEMPO). Protein expression level was determined by Western blot, cellular observation by transmission electron microscope and ROS production by functional analysis kits. Salidroside reduced IR and activated insulin signaling along with the stimulation of AMPK/SIRT1 signaling and downstream regulation of MQC and ROS production. These salidroside effects were comparable to those of AICAR and could be prevented by AMPK/SIRT1 inhibitors or siRNAs, respectively. Salidroside reduces IR and regulates MQC and ROS production by activating AMPK/SIRT1 signaling pathway. Since IR is a critical issue for public health, to explore a potent agent against IR is of high interest. The anti-IR effects of salidroside warrant further experimental and clinical studies.


2020 ◽  
Vol 21 (1) ◽  
pp. 66-77 ◽  
Author(s):  
Luping Yang ◽  
Yijing Jiang ◽  
Lihong Shi ◽  
Dongling Zhong ◽  
Yuxi Li ◽  
...  

Alzheimer's disease (AD) is the most common neurodegenerative disorder. The pathogenesis of AD is very complicated. For decades, the amyloid hypothesis has influenced and guided research in the field of AD. Meanwhile, researchers gradually realized that AD is caused by multiple concomitant factors, such as autophagy, mitochondrial quality control, insulin resistance and oxidative stress. In current clinical trials, the improvement strategies of AD, such as Aβ antibody immunotherapy and gamma secretase inhibitors, are limited. There is mounting evidence of neurodegenerative disorders indicated that activation of AMP-activated protein kinase (AMPK) may have broad neuroprotective effects. We reviewed the researches on AMPK for AD, the results demonstrated that activation of AMPK is controversial in Aβ deposition and tau phosphorylation, but is positive to promote autophagy, maintain mitochondrial quality control, reduce insulin resistance and relieve oxidative stress. It is concluded that AMPK might be a new target for AD by aggressively treating the risk factors in the future.


2019 ◽  
Vol 99 (12) ◽  
pp. 1795-1809 ◽  
Author(s):  
Jia Shi ◽  
Jianbo Yu ◽  
Yuan Zhang ◽  
Lili Wu ◽  
Shuan Dong ◽  
...  

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 371
Author(s):  
Filipa Barroso Gonçalves ◽  
Vanessa Alexandra Morais

Mitochondria are known as highly dynamic organelles essential for energy production. Intriguingly, in the recent years, mitochondria have revealed the ability to maintain cell homeostasis and ultimately regulate cell fate. This regulation is achieved by evoking mitochondrial quality control pathways that are capable of sensing the overall status of the cellular environment. In a first instance, actions to maintain a robust pool of mitochondria take place; however, if unsuccessful, measures that lead to overall cell death occur. One of the central key players of these mitochondrial quality control pathways is PINK1 (PTEN-induce putative kinase), a mitochondrial targeted kinase. PINK1 is known to interact with several substrates to regulate mitochondrial functions, and not only is responsible for triggering mitochondrial clearance via mitophagy, but also participates in maintenance of mitochondrial functions and homeostasis, under healthy conditions. Moreover, PINK1 has been associated with the familial form of Parkinson’s disease (PD). Growing evidence has strongly linked mitochondrial homeostasis to the central nervous system (CNS), a system that is replenished with high energy demanding long-lasting neuronal cells. Moreover, sporadic cases of PD have also revealed mitochondrial impairments. Thus, one could speculate that mitochondrial homeostasis is the common denominator in these two forms of the disease, and PINK1 may play a central role in maintaining mitochondrial homeostasis. In this review, we will discuss the role of PINK1 in the mitochondrial physiology and scrutinize its role in the cascade of PD pathology.


Cell ◽  
2021 ◽  
Vol 184 (11) ◽  
pp. 2896-2910.e13
Author(s):  
Haifeng Jiao ◽  
Dong Jiang ◽  
Xiaoyu Hu ◽  
Wanqing Du ◽  
Liangliang Ji ◽  
...  

Author(s):  
Roberta A. Gottlieb ◽  
Honit Piplani ◽  
Jon Sin ◽  
Savannah Sawaged ◽  
Syed M. Hamid ◽  
...  

AbstractMitochondrial quality control depends upon selective elimination of damaged mitochondria, replacement by mitochondrial biogenesis, redistribution of mitochondrial components across the network by fusion, and segregation of damaged mitochondria by fission prior to mitophagy. In this review, we focus on mitochondrial dynamics (fusion/fission), mitophagy, and other mechanisms supporting mitochondrial quality control including maintenance of mtDNA and the mitochondrial unfolded protein response, particularly in the context of the heart.


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