PXD027901

PXD027901 is an original dataset announced via ProteomeXchange.

Title	Pharmacological inhibition of mitochondrial soluble adenylyl cyclase in astrocytes causes activation of AMP-activated protein kinase and induces breakdown of glycogen
Description	Astrocytes contain the majority of the brain’s supply of glycogen which has been suggested to play an important role in neuronal synaptic plasticity. This may be mediated by release of glycogen-derived lactate or glutamine supporting neuronal metabolism or via induction of neuronal signaling pathways. The second messenger cyclic AMP (cAMP) can induce glycogen breakdown and activation of cytosolic soluble adenylyl cyclase (sAC) in astrocytes has been suggested to be the link between neuronal depolarization and glycogen breakdown. However, recent studies have revealed that sAC residing in the mitochondria rather than the cytosol is regulating mitochondrial bioenergetics, and that employing pharmacological inhibitors of sAC significantly alters cellular energy metabolism. This effect on energy metabolism could influence the interpretation of previous studies employing pharmacological inhibition of sAC. Here, we show that pharmacological inhibition of sAC lowers mitochondrial respiration, induces phosphorylation of the metabolic master switch AMPK, and decreases glycogen stores in cultured astrocytes. In light of this, we discuss the pharmacological challenges of investigating the functional and metabolic roles of sAC in astrocytes.
HostingRepository	PRIDE
AnnounceDate	2021-08-13
AnnouncementXML	Submission_2021-08-13_04:06:26.380.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD027901
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Martin R. Larsen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Acyrthosiphon pisum (Pea aphid); NCBI TaxID: 7029;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-12 14:24:06	ID requested
⏵ 1	2021-08-13 04:06:27	announced

Jakobsen E, Andersen JV, Christensen SK, Siamka O, Larsen MR, Waagepetersen HS, Aldana BI, Bak LK, Pharmacological inhibition of mitochondrial soluble adenylyl cyclase in astrocytes causes activation of AMP-activated protein kinase and induces breakdown of glycogen. Glia, 69(12):2828-2844(2021) [pubmed]

submitter keyword: Mouse Astrocytes, adenylyl cyclase, Phosphorylation, AMP-activated protein kinase, energy metabolism

Martin R. Larsen
contact affiliation	Department of Biochemistry and Molecular Biology University of Southern Denmark Campusvej 55 DK-5230 Odense M Denmark
contact email	mrl@bmb.sdu.dk
lab head
Martin R. Larsen
contact affiliation	University of Southern Denmark
contact email	mrl@bmb.sdu.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027901
     1. Label: PRIDE project
     2. Name: Pharmacological inhibition of mitochondrial soluble adenylyl cyclase in astrocytes causes activation of AMP-activated protein kinase and induces breakdown of glycogen