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The Soluble Adenylyl Cyclase Inhibitor LRE1 Prevents Hepatic Ischemia/Reperfusion Damage Through Improvement of Mitochondrial Function

Title data

Teodoro, Joao S. ; Amorim, Joao A. ; Machado, Ivo F. ; Castela, Ana C. ; Steegborn, Clemens ; Sinclair, David A. ; Rolo, Anabel P. ; Palmeira, Carlos M.:
The Soluble Adenylyl Cyclase Inhibitor LRE1 Prevents Hepatic Ischemia/Reperfusion Damage Through Improvement of Mitochondrial Function.
In: International Journal of Molecular Sciences. Vol. 21 (July 2020) Issue 14 . - No. 4896.
ISSN 1422-0067
DOI: https://doi.org/10.3390/ijms21144896

Abstract in another language

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.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: LRE1; Ischemia/reperfusion; Liver; Mitochondria; Sirtuin 3; Soluble adenylyl cyclase
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Clemens Steegborn
Result of work at the UBT: No
DDC Subjects: 500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 07 Sep 2020 07:46
Last Modified: 07 Sep 2020 07:46
URI: https://eref.uni-bayreuth.de/id/eprint/56811