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Title: The Soluble Adenylyl Cyclase Inhibitor LRE1 Prevents Hepatic Ischemia/Reperfusion Damage Through Improvement of Mitochondrial Function
Authors: Teodoro, João S. 
Amorim, João A. 
Machado, Ivo F. 
Castela, Ana C. 
Steegborn, Clemens
Sinclair, David A
Rolo, Anabela P. 
Palmeira, Carlos M. 
Keywords: mitochondria; ischemia/reperfusion; liver; soluble adenylyl cyclase; LRE1; sirtuin 3
Issue Date: 11-Jul-2020
Publisher: MDPI
Serial title, monograph or event: International Journal of Molecular Sciences
Volume: 21
Issue: 14
Abstract: Hepatic ischemia/reperfusion (I/R) injury is a leading cause of organ dysfunction and failure in numerous pathological and surgical settings. At the core of this issue lies mitochondrial dysfunction. Hence, strategies that prime mitochondria towards damage resilience might prove applicable in a clinical setting. A promising approach has been to induce a mitohormetic response, removing less capable organelles, and replacing them with more competent ones, in preparation for an insult. Recently, a soluble form of adenylyl cyclase (sAC) has been shown to exist within mitochondria, the activation of which improved mitochondrial function. Here, we sought to understand if inhibiting mitochondrial sAC would elicit mitohormesis and protect the liver from I/R injury. Wistar male rats were pretreated with LRE1, a specific sAC inhibitor, prior to the induction of hepatic I/R injury, after which mitochondria were collected and their metabolic function was assessed. We find LRE1 to be an effective inducer of a mitohormetic response based on all parameters tested, a phenomenon that appears to require the activity of the NAD+-dependent sirtuin deacylase (SirT3) and the subsequent deacetylation of mitochondrial proteins. We conclude that LRE1 pretreatment leads to a mitohormetic response that protects mitochondrial function during I/R injury.
ISSN: 1422-0067
DOI: 10.3390/ijms21144896
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais

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