Ca<sup>2+</sup> and cAMP cross‐talk in mitochondria

Benedetto, Giulietta Di; Pendin, Diana; Greotti, Elisa; Pizzo, Paola; Pozzan, Tullio

doi:10.1113/jphysiol.2013.259135

Cited by 42 publications

(38 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The requisite regulator of PKA, cyclic adenosine monophosphate (cAMP), was once thought to diffuse from the cytosol; however, cAMP can be produced in mitochondria by an endogenous bicarbonate-sensitive adenylyl cyclase (Acin-Perez et al 2009;Di Benedetto et al 2014). While it remains unclear how PKA enters mitochondria, its distribution within the organelle is very likely under the control of A-kinase anchoring proteins (AKAPs), which target the regulatory subunit of PKAs and direct them to specific sites (see Michel and Scott 2002).…”

Section: Phosphorylation Of Cox Subunitsmentioning

confidence: 98%

“…Mitochondrial PKA is distributed throughout the organelle, from the outer and inner mitochondrial membranes to the intermembrane space and the matrix. The PKA associated with the outer mitochondrial membrane may be involved in apoptosis, whereas matrix PKA matrix may phosphorylate the OXPHOS complexes (see Di Benedetto et al 2014).…”

Section: Phosphorylation Of Cox Subunitsmentioning

confidence: 99%

See 1 more Smart Citation

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Bremer

SniderT.

2014

Can. J. Zool.

View full text Add to dashboard Cite

Modification of mitochondrial content demands the synthesis of hundreds of proteins encoded by nuclear and mitochondrial genomes. The responsibility for coordination of this process falls to nuclear-encoded master regulators of transcription. DNAbinding proteins and coactivators integrate information from energy-sensing pathways and hormones to alter mitochondrial gene expression. In mammals, the signaling cascade for mitochondrial biogenesis can be described as follows: hormonal signals and energetic information are sensed by protein-modifying enzymes that in turn regulate the post-translational modification of transcription factors. Once activated, transcription-factor complexes form on promoter elements of many of the nuclear-encoded mitochondrial genes, recruiting proteins that remodel chromatin and initiate transcription. One master regulator in mammals, PGC-1␣, is well studied because of its role in determining the metabolic phenotype of muscles, but also due to its importance in mitochondria-related metabolic diseases. However, relatively little is known about the role of this pathway in other vertebrates. These uncertainties raise broader questions about the evolutionary origins of the pathway and its role in generating the diversity in muscle metabolic phenotypes seen in nature.Résumé : La modification du contenu mitochondrial nécessite la synthèse de centaines de protéines encodées par les génomes nucléaire et mitochondrial, la coordination de ce processus étant assurée par des maîtres régulateurs de la transcription codés par le génome nucléaire. Des protéines se liant à l'ADN et des coactivateurs intègrent l'information provenant de voies de détection de l'énergie et d'hormones pour ensuite modifier l'expression des gènes mitochondriaux. Chez les mammifères, la cascade de signalisation pour la biogénèse mitochondriale peut être décrite comme suit : des enzymes de modification de protéines détectent des signaux hormonaux et de l'information énergétique et régulent la modification post-traduction des facteurs de transcription. Une fois activés, des complexes de facteurs de transcription se forment sur des éléments promoteurs de nombreux gènes mitochondriaux à encodage nucléaire, recrutant des protéines qui remodèlent la chromatine et amorcent la transcription. Un des maîtres régulateurs chez les mammifères, le PGC-1␣, fait l'objet de nombreuses études en raison de son rôle dans la détermination du phénotype métabolique des muscles, mais aussi en raison de son importance dans les maladies métaboliques associées aux mitochondries. Les connaissances sur le rôle de cette voie chez d'autres vertébrés sont toutefois limitées. Ces incertitudes soulèvent des questions plus larges concernant les origines évolutives de cette voie et son rôle dans la production de la diversité de phénotypes métaboliques musculaires observée dans la nature. [Traduit par la Rédaction]

show abstract

Section: Phosphorylation Of Cox Subunitsmentioning

confidence: 98%

Section: Phosphorylation Of Cox Subunitsmentioning

confidence: 99%

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Bremer

SniderT.

2014

Can. J. Zool.

View full text Add to dashboard Cite

show abstract

“…It is certainly an interesting finding that the physiology of the two major cell regulators Ca 2+ and cAMP takes place inside the mitochondria with interconnected pathway [25]. …”

Section: Sac Regulation By Ca2+ In Mitochondriamentioning

confidence: 99%

“…Di Benedetto et al reported failure to show mitochondrial localization of GFP tagged PKA subunits (unpublished results in [25]). Furthermore, PKA activity could not be measured by matrix targeted A-kinase activity reporter (AKAR) 3 and 4 [18].…”

Section: Sac-camp Effectors In Mitochondriamentioning

confidence: 99%

Role of soluble adenylyl cyclase in mitochondria

Valsecchi

Konràd

Manfredi

2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

The soluble adenylyl cyclase (sAC) catalyzes the conversion of ATP into cyclic AMP (cAMP). Recent studies have shed new light on the role of sAC localized in mitochondria and its product cAMP, which drives mitochondrial protein phosphorylation and regulation of the oxidative phosphorylation system and other metabolic enzymes, presumably through the activation of intra-mitochondrial PKA. In this review article, we summarize recent findings on mitochondrial sAC activation by bicarbonate (HCO3−) and calcium (Ca2+) and the effects on mitochondrial metabolism. We also discuss putative mechanisms whereby sAC-mediated mitochondrial protein phosphorylation regulates mitochondrial metabolism.

show abstract

“…[33][34][35] However, the long-standing puzzle of how mitochondria pick up Ca 2+ using the low-affinity MCU has been solved only recently. Pioneering studies proposed a model where microdomains of high [Ca 2+ ] are formed by the release of the ion from the lumen of the ER directly on the mitochondrial surface at sites of close proximity between these organelles.…”

mentioning

confidence: 99%

The coming of age of the mitochondria–ER contact: a matter of thickness

2016

View full text Add to dashboard Cite

The sites of near-contact between the mitochondrion and the endoplasmic reticulum (ER) have earned a lot of attention due to their key role in the maintenance of lipid and calcium (Ca 2+ ) homeostasis, in the initiation of autophagy and mitochondrial division, and in sensing metabolic shifts. At these sites, typically called MAMs (mitochondria-associated ER membranes) or MERCs (mitochondria-ER contacts), the organelles juxtapose at a distance that can range from~10 to~50 nm. The multifunctional role of this subcellular compartment is puzzling; further, recent studies have shown that mitochondria-ER contacts are highly plastic structures that remodel upon metabolic transitions and that their activity in controlling lipid homeostasis could be involved in Alzheimer's disease pathogenesis. This review aims at integrating the functions of this subcellular compartment to its most characterizing and unexplored structural parameter, their 'thickness': that is, the width of the cleft that separates the cytosolic face of the outer mitochondrial membrane from that of the ER. We describe and discuss the reasons why the thickness of a MERC should be considered a regulated structural parameter of the cell that defines and controls its function. Further, we propose a MERC classification that will help organize the expanding field of MERCs biology and of their role in cell physiology and human disease.

show abstract

Ca²⁺ and cAMP cross‐talk in mitochondria

Cited by 42 publications

References 44 publications

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Role of soluble adenylyl cyclase in mitochondria

The coming of age of the mitochondria–ER contact: a matter of thickness

Contact Info

Product

Resources

About

Ca2+ and cAMP cross‐talk in mitochondria

Cited by 42 publications

References 44 publications

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Role of soluble adenylyl cyclase in mitochondria

The coming of age of the mitochondria–ER contact: a matter of thickness

Contact Info

Product

Resources

About

Ca²⁺ and cAMP cross‐talk in mitochondria