Mitochondrial Signaling and Neurodegeneration

2016 ◽  
pp. 107-137 ◽  
Author(s):  
Martin Picard ◽  
Meagan J. McManus
Keyword(s):  
Mitochondrial Signaling

scholarly journals Role of the Mitochondrial Signaling Pathway in Murine Coronavirus-Induced Oligodendrocyte Apoptosis

2006 ◽  
Vol 80 (1) ◽  
pp. 395-403 ◽  
Author(s):  
Yin Liu ◽  
Yinghui Pu ◽  
Xuming Zhang
Keyword(s):  
Hepatitis Virus ◽  
Mitochondrial Pathway ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Antiapoptotic Proteins ◽  
Mitochondrial Signaling ◽  
Drastic Increase ◽  
Infected Cells

ABSTRACT A previous study demonstrated that infection of rat oligodendrocytes by mouse hepatitis virus (MHV) resulted in apoptosis, which is caspase dependent (Y. Liu, Y. Cai, and X. Zhang, J. Virol. 77:11952-11963, 2003). Here we determined the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis. We found that caspase-9 activity was 12-fold higher in virus-infected cells than in mock-infected cells at 24 h postinfection (p.i.). Pretreatment of cells with a caspase-9 inhibitor completely blocked caspase-9 activation and partially inhibited the apoptosis mediated by MHV infection. Analyses of cytochrome c release further revealed an activation of the mitochondrial apoptotic pathway. Stable overexpression of the two antiapoptotic proteins Bcl-2 and Bcl-xL significantly, though only partially, blocked apoptosis, suggesting that activation of the mitochondrial pathway is partially responsible for the apoptosis. To identify upstream signals, we determined caspase-8 activity, cleavage of Bid, and expression of Bax and Bad by Western blotting. We found a drastic increase in caspase-8 activity and cleavage of Bid at 24 h p.i. in virus-infected cells, suggesting that Bid may serve as a messenger to relay the signals from caspase-8 to mitochondria. However, treatment with a caspase-8 inhibitor only slightly blocked cytochrome c release from the mitochondria. Furthermore, we found that Bax but not Bad was significantly increased at 12 h p.i. in cells infected with both live and UV-inactivated viruses and that Bax activation was partially blocked by treatment with the caspase-8 inhibitor. These results thus establish the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis.

Microcystin-LR induces angiodysplasia and vascular dysfunction through promoting cell apoptosis by the mitochondrial signaling pathway

Chemosphere ◽  
2019 ◽  
Vol 218 ◽  
pp. 438-448 ◽  
Author(s):  
Qilong Wang ◽  
Yuanli Liu ◽  
Jingsong Guo ◽  
Song Lin ◽  
Yeqi Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Vascular Dysfunction ◽  
Mitochondrial Signaling

scholarly journals N-acetyl Cysteine, Selenium, and Ascorbic Acid Rescue Diabetic Cardiac Hypertrophy via Mitochondrial-Associated Redox Regulators

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7285
Author(s):  
Iram Mushtaq ◽  
Zainab Bashir ◽  
Mehvish Sarwar ◽  
Maria Arshad ◽  
Ayesha Ishtiaq ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Cardiac Hypertrophy ◽  
Diabetic Rats ◽  
Glucose Measurement ◽  
Heart Weight ◽  
Cardiac Complications ◽  
Myocardial Stiffness ◽  
Expression Levels ◽  
Mitochondrial Signaling ◽  
Acetyl Cysteine

Metabolic disorders often lead to cardiac complications. Metabolic deregulations during diabetic conditions are linked to mitochondrial dysfunctions, which are the key contributing factors in cardiac hypertrophy. However, the underlying mechanisms involved in diabetes-induced cardiac hypertrophy are poorly understood. In the current study, we initially established a diabetic rat model by alloxan-administration, which was validated by peripheral glucose measurement. Diabetic rats displayed myocardial stiffness and fibrosis, changes in heart weight/body weight, heart weight/tibia length ratios, and enhanced size of myocytes, which altogether demonstrated the establishment of diabetic cardiac hypertrophy (DCH). Furthermore, we examined the expression of genes associated with mitochondrial signaling impairment. Our data show that the expression of PGC-1α, cytochrome c, MFN-2, and Drp-1 was deregulated. Mitochondrial-signaling impairment was further validated by redox-system dysregulation, which showed a significant increase in ROS and thiobarbituric acid reactive substances, both in serum and heart tissue, whereas the superoxide dismutase, catalase, and glutathione levels were decreased. Additionally, the expression levels of pro-apoptotic gene PUMA and stress marker GATA-4 genes were elevated, whereas ARC, PPARα, and Bcl-2 expression levels were decreased in the heart tissues of diabetic rats. Importantly, these alloxan-induced impairments were rescued by N-acetyl cysteine, ascorbic acid, and selenium treatment. This was demonstrated by the amelioration of myocardial stiffness, fibrosis, mitochondrial gene expression, lipid profile, restoration of myocyte size, reduced oxidative stress, and the activation of enzymes associated with antioxidant activities. Altogether, these data indicate that the improvement of mitochondrial dysfunction by protective agents such as N-acetyl cysteine, selenium, and ascorbic acid could rescue diabetes-associated cardiac complications, including DCH.

scholarly journals Deletion of Bmal1 Impairs Pancreatic β-Cell Function via Mitochondrial Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Lu Ye ◽  
Huaxiang Wu ◽  
Weihong Xu
Keyword(s):  
Signaling Pathway ◽  
Cell Function ◽  
Mitofusin 2 ◽  
Insulinoma Cell ◽  
Mitochondrial Signaling ◽  
Β Cell Function ◽  
Mrna And Protein Expression ◽  
Glucose Stimulated Insulin Secretion ◽  
Mitofusin 1 ◽  
Interfering Rna

Several studies have demonstrated that brain and muscle Arnt-like protein-1 (Bmal1) acts as a core clock gene for maintaining normal cell function, including hepatocytes and cardiomyocytes. Loss of Bmal1 is associated with type 2 diabetes due to pancreatic β-cell failure. However, little information is available about its role and mechanism in pancreatic β-cell. To address this, we investigated the consequences of Bmal1 inhibition in an insulinoma cell line (INS-1) by using small interfering RNA (siRNA). We observed that knockout of Bmal1 impaired glucose-stimulated insulin secretion in β-cell. Meanwhile, the depletion of Bmal1 in β-cell caused an adverse change in mitochondrial membrane potential and mitochondrial architecture. Deletion of Bmal1 attenuated mRNA and protein expression of mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2) and enhanced the expression of fission 1 (Fis1). In summary, the deletion of Bmal1 impaired β-cell function may be via the mitochondrial signaling pathway in INS-1 cells.

scholarly journals Mitochondrial fragmentation enables localized signaling required for cell repair

2020 ◽  
Vol 219 (5) ◽  
Author(s):  
Adam Horn ◽  
Shreya Raavicharla ◽  
Sonna Shah ◽  
Dan Cox ◽  
Jyoti K. Jaiswal
Keyword(s):  
Plasma Membrane ◽  
Calcium Influx ◽  
Cell Damage ◽  
Mitochondrial Fission ◽  
Adaptor Protein ◽  
Mitochondrial Fragmentation ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Mitochondrial Signaling ◽  
Plasma Membrane Repair

Plasma membrane injury can cause lethal influx of calcium, but cells survive by mounting a polarized repair response targeted to the wound site. Mitochondrial signaling within seconds after injury enables this response. However, as mitochondria are distributed throughout the cell in an interconnected network, it is unclear how they generate a spatially restricted signal to repair the plasma membrane wound. Here we show that calcium influx and Drp1-mediated, rapid mitochondrial fission at the injury site help polarize the repair response. Fission of injury-proximal mitochondria allows for greater amplitude and duration of calcium increase in these mitochondria, allowing them to generate local redox signaling required for plasma membrane repair. Drp1 knockout cells and patient cells lacking the Drp1 adaptor protein MiD49 fail to undergo injury-triggered mitochondrial fission, preventing polarized mitochondrial calcium increase and plasma membrane repair. Although mitochondrial fission is considered to be an indicator of cell damage and death, our findings identify that mitochondrial fission generates localized signaling required for cell survival.

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