Abstract
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′-cyclic 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.
Highlights
We focus on the role of soluble adenylyl cyclase (sAC)-dependent cyclic adenosine monophosphate (cAMP) signalling in regulating mitochondrial homeostasis
Similar to our study [76], results published by Wang et al [29] revealed that stimulation of endogenous sAC with HCO3 − as well as overexpression of sAC prevented the death of neonatal cardiomyocytes induced by camptothecin, H2 O2 or TNF-α+actinomycin D
Dysregulation of mitochondrial homeostasis may lead to severe diseases like cancer, neurodegenerative and cardiovascular diseases, diabetes, and inflammation
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. CAMP signalling consists of three components: (i) enzymes synthesizing cAMP, i.e., adenylyl cyclases; (ii) enzymes degrading cAMP, i.e., phosphodiesterases (PDEs); and (iii) effectors such as protein kinase A (PKA), exchange protein directly activated by cAMP (EPAC), and cyclic nucleotide-gated ion channels. The localization of tmAC is restricted to the plasma membrane, whereas sAC is widely distributed within the cell and inside organelles [8]. SAC forms cAMP pools within various cellular compartments, e.g., the cytosol, mitochondria, the nucleus, or the subplasmalemmal compartment [15,16,17,18] Such distinct subcellular distribution allows specific regulation of various cellular functions such as cell death and growth [19], migration [18], gene expression [20], and ATP synthesis [21]. We discuss the impact of the dysregulation of sAC signalling on mitochondrial biology and its relation to various diseases
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