Regulation of AMPK activity by type 10 adenylyl cyclase: contribution to the mitochondrial biology, cellular redox and energy homeostasis

Jayarajan, Vignesh; Appukuttan, Avinash; Aslam, Muhammad; Reusch, Peter; Regitz‐Zagrosek, Vera; Ladilov, Yury

doi:10.1007/s00018-019-03152-y

Cited by 24 publications

(22 citation statements)

References 54 publications

(84 reference statements)

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“…In agreement with this study, we have recently revealed that sAC knockdown leads to a significant down-regulation of mitochondrial clearance in cardiac and endothelial cells [ 74 ]. These effects were associated with reduced lysosomal acidification and autophagosome accumulation (unpublished data), indicating disturbed autophagy flow due to lysosomal dysfunction.…”

Section: Role Of Sac In Lysosomal Functionsupporting

confidence: 89%

“…Since V-ATPase leads to acidification of both endosomes and lysosomes, suppression of sAC, and, in turn, V-ATPase activity, may impair autophagy due to lysosomal dysfunction. Our recent studies support this idea by demonstrating that sAC inhibition or knockdown disturbs mitophagy in endothelial and cardiac cells [ 74 ], reduces lysosomal acidification, and leads to autophagosome accumulation (unpublished data). Furthermore, several studies have demonstrated the positive effects of cAMP elevation on the autophagy machinery [ 77 , 79 , 80 ].…”

Section: Role Of Sac In Autophagymentioning

confidence: 58%

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Targeting the sAC-Dependent cAMP Pool to Prevent SARS-Cov-2 Infection

Aslam

Ladilov²

2020

Cells

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An outbreak of the novel coronavirus (CoV) SARS-CoV-2, the causative agent of COVID-19 respiratory disease, infected millions of people since the end of 2019, led to high-level morbidity and mortality and caused worldwide social and economic disruption. There are currently no antiviral drugs available with proven efficacy or vaccines for its prevention. An understanding of the underlying cellular mechanisms involved in virus replication is essential for repurposing the existing drugs and/or the discovery of new ones. Endocytosis is the important mechanism of entry of CoVs into host cells. Endosomal maturation followed by the fusion with lysosomes are crucial events in endocytosis. Late endosomes and lysosomes are characterized by their acidic pH, which is generated by a proton transporter V-ATPase and required for virus entry via endocytic pathway. The cytoplasmic cAMP pool produced by soluble adenylyl cyclase (sAC) promotes V-ATPase recruitment to endosomes/lysosomes and thus their acidification. In this review, we discuss targeting the sAC-specific cAMP pool as a potential strategy to impair the endocytic entry of the SARS-CoV-2 into the host cell. Furthermore, we consider the potential impact of sAC inhibition on CoV-induced disease via modulation of autophagy and apoptosis.

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Section: Role Of Sac In Lysosomal Functionsupporting

confidence: 89%

Section: Role Of Sac In Autophagymentioning

confidence: 58%

Targeting the sAC-Dependent cAMP Pool to Prevent SARS-Cov-2 Infection

Aslam

Ladilov²

2020

Cells

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“…Our recent report [66] showed a direct link between sAC and mitophagy in cardiac and endothelial cells. Particularly, downregulation of sAC led to the disturbed mitochondrial clearance that culminated in oxidative stress and energy imbalance.…”

Section: Sac and Mitophagymentioning

confidence: 87%

Regulation of Mitochondrial Homeostasis by sAC-Derived cAMP Pool: Basic and Translational Aspects

Aslam

Ladilov

2021

Cells

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In contrast to the traditional view of mitochondria being solely a source of cellular energy, e.g., the “powerhouse” of the cell, mitochondria are now known to be key regulators of numerous cellular processes. Accordingly, disturbance of mitochondrial homeostasis is a basic mechanism in several pathologies. Emerging data demonstrate that 3′–5′-yclic adenosine monophosphate (cAMP) signalling plays a key role in mitochondrial biology and homeostasis. Mitochondria are equipped with an endogenous cAMP synthesis system involving soluble adenylyl cyclase (sAC), which localizes in the mitochondrial matrix and regulates mitochondrial function. Furthermore, sAC localized at the outer mitochondrial membrane contributes significantly to mitochondrial biology. Disturbance of the sAC-dependent cAMP pools within mitochondria leads to mitochondrial dysfunction and pathology. In this review, we discuss the available data concerning the role of sAC in regulating mitochondrial biology in relation to diseases.

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“…BioMed Research International energy balance in the cell [50]. In our model, both FSK induce overexpression of both AC and AMPK in adipose tissue of dyslipidemic rats.…”

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confidence: 89%

Synergetic Action of Forskolin and Mevastatin Induce Normalization of Lipids Profile in Dyslipidemic Rats through Adenosine Monophosphate Kinase Upregulation

Abdelazim

Ismail

Abumaghaid

et al. 2021

BioMed Research International

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In the present study, we examined the synergetic effect of forskolin and mevastatin administration on lipid profile and lipid metabolism in omental adipose tissue in dyslipidemic rats. The study was conducted on forty male albino rats. The rats were randomly classified into four main groups of ten animals in each group as follows: group A, served as control nontreated; group B, rats that received Triton WR 1339 (500 mg/kg); group C, rats that received Triton WR 1339 with forskolin (100% FSK extract 0.5 mg/kg/day) for four weeks; and group D, dyslipidemic rats received both mevastatin and forskolin. At the end of the experimental period, blood and omental adipose tissue samples were collected, preserved, and used for biochemical determination of lipid profile and mRNA expression profile of adenylate cyclase (AC), hormone-sensitive lipase, respectively (HSL), and adenosine monophosphate-activated protein kinase (AMPK). The results showed a significant decline in the serum concentration of total cholesterol, LDL-cholesterol, and triglycerides, although there was a significant increase in serum levels of HDL-cholesterol and glycerol in rats received forskolin alone or with mevastatin when compared with control and dyslipidemic groups. The mRNA expression levels of AC, HSL, and AMPK were significantly increased in omental adipose tissue of rats received forskolin when compared with other groups. In conclusion, forskolin acts synergistically with mevastatin to lower lipid profile and improve lipid metabolism in dyslipidemic rats through upregulation of AMPK expression.

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Regulation of AMPK activity by type 10 adenylyl cyclase: contribution to the mitochondrial biology, cellular redox and energy homeostasis

Cited by 24 publications

References 54 publications

Targeting the sAC-Dependent cAMP Pool to Prevent SARS-Cov-2 Infection

Targeting the sAC-Dependent cAMP Pool to Prevent SARS-Cov-2 Infection

Regulation of Mitochondrial Homeostasis by sAC-Derived cAMP Pool: Basic and Translational Aspects

Synergetic Action of Forskolin and Mevastatin Induce Normalization of Lipids Profile in Dyslipidemic Rats through Adenosine Monophosphate Kinase Upregulation

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