Liepinsh 2021 Free Radic Biol Med

Liepinsh E, Kuka J, Vilks K, Svalbe B, Stelfa G, Vilskersts R, Sevostjanovs E, Goldins NR, Groma V, Grinberga S, Plaas M, Makrecka-Kuka M, Dambrova M (2021) Low cardiac content of long-chain acylcarnitines in TMLHE knockout mice prevents ischaemia-reperfusion-induced mitochondrial and cardiac damage. Free Radic Biol Med 177:370-80.

» PMID: 34728372 Open Access

Liepinsh Edgars, Kuka Janis, Vilks Karlis, Svalbe Baiba, Stelfa Gundega, Vilskersts Reinis, Sevostjanovs Eduards, Goldins Niks Ricards, Groma Valerija, Grinberga Solveiga, Plaas Mario, Makrecka-Kuka Marina, Dambrova Maija (2021) Free Radic Biol Med

Abstract: Increased tissue content of long-chain acylcarnitines may induce mitochondrial and cardiac damage by stimulating ROS production. N⁶-trimethyllysine dioxygenase (TMLD) is the first enzyme in the carnitine/acylcarnitine biosynthesis pathway. Inactivation of the TMLHE gene (TMLHE KO) in mice is expected to limit long-chain acylcarnitine synthesis and thus induce a cardio- and mitochondria-protective phenotype. TMLHE gene deletion in male mice lowered acylcarnitine concentrations in blood and cardiac tissues by up to 85% and decreased fatty acid oxidation by 30% but did not affect muscle and heart function in mice. Metabolome profile analysis revealed increased levels of polyunsaturated fatty acids (PUFAs) and a global shift in fatty acid content from saturated to unsaturated lipids. In the risk area of ischemic hearts in TMLHE KO mouse, the OXPHOS-dependent respiration rate and OXPHOS coupling efficiency were fully preserved. Additionally, the decreased long-chain acylcarnitine synthesis rate in TMLHE KO mice prevented ischaemia-reperfusion-induced ROS production in cardiac mitochondria. This was associated with a 39% smaller infarct size in the TMLHE KO mice. The arrest of the acylcarnitine biosynthesis pathway in TMLHE KO mice prevents ischaemia-reperfusion-induced damage in cardiac mitochondria and decreases infarct size. These results confirm that the decreased accumulation of ROS-increasing fatty acid metabolism intermediates prevents mitochondrial and cardiac damage during ischaemia-reperfusion. • Keywords: Acylcarnitine, Fatty acid metabolism, Gamma-butyrobetaine, Myocardial infarction, PUFA, Trimethyllysine • Bioblast editor: Plangger M • O2k-Network Lab: LV Riga Makrecka-Kuka M

On terminology

» Mitochondrial states and rates - terminology beyond MitoEAGLE 2020

For harmonization of terminology on respiratory states and rates, see

• Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. https://doi.org/10.26124/bec:2020-0001.v1

Labels:

MitoEAGLE terminology 

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Stress:Ischemia-reperfusion  Organism: Mouse  Tissue;cell: Heart  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k 

2021-11