Cardiac myocyte-specific knock-out of calcium-independent phospholipase A2γ (iPLA2γ) decreases oxidized fatty acids during ischemia/reperfusion and reduces infarct size

Calcium-independent phospholipase A(2)γ (iPLA(2)γ) is a mitochondrial enzyme that produces lipid second messengers that facilitate opening of the mitochondrial permeability transition pore (mPTP) and contribute to the production of oxidized fatty acids in myocardium. To specifically identify the roles of iPLA(2)γ in cardiac myocytes, we generated cardiac myocyte-specific iPLA(2)γ knock-out (CMiPLA(2)γKO) mice by removing the exon encoding the active site serine (Ser-477). Hearts of CMiPLA(2)γKO mice exhibited normal hemodynamic function, glycerophospholipid molecular species composition, and normal rates of mitochondrial respiration and ATP production. In contrast, CMiPLA(2)γKO mice demonstrated attenuated Ca(2+)-induced mPTP opening that could be rapidly restored by the addition of palmitate and substantially reduced production of oxidized polyunsaturated fatty acids (PUFAs). Furthermore, myocardial ischemia/reperfusion (I/R) in CMiPLA(2)γKO mice (30 min of ischemia followed by 30 min of reperfusion in vivo) dramatically decreased oxidized fatty acid production in the ischemic border zones. Moreover, CMiPLA(2)γKO mice subjected to 30 min of ischemia followed by 24 h of reperfusion in vivo developed substantially less cardiac necrosis in the area-at-risk in comparison with their WT littermates. Furthermore, we found that membrane depolarization in murine heart mitochondria was sensitized to Ca(2+) by the presence of oxidized PUFAs. Because mitochondrial membrane depolarization and calcium are known to activate iPLA(2)γ, these results are consistent with salvage of myocardium after I/R by iPLA(2)γ loss of function through decreasing mPTP opening, diminishing production of proinflammatory oxidized fatty acids, and attenuating the deleterious effects of abrupt increases in calcium ion on membrane potential during reperfusion

Genetic deletion of skeletal muscle iPLA2γ results in mitochondrial dysfunction, muscle atrophy and alterations in whole-body energy metabolism

Skeletal muscle is the major site of glucose utilization in mammals integrating serum glucose clearance with mitochondrial respiration. To mechanistically elucidate the roles of iPL

100 essential questions for the future of agriculture

Publication history: Accepted - 8 March 2023; Published online - 11 April 2023.The world is at a crossroad when it comes to agriculture. The global population is growing, and the demand for food is increasing, putting a strain on our agricultural resources and practices. To address this challenge, innovative, sustainable, and inclusive approaches to agriculture are urgently required. In this paper, we launched a call for Essential Questions for the Future of Agriculture and identified a priority list of 100 questions. We focus on 10 primary themes: transforming agri-food systems, enhancing resilience of agriculture to climate change, mitigating climate change through agriculture, exploring resources and technologies for breeding, advancing cultivation methods, sustaining healthy agroecosystems, enabling smart and controlled-environment agriculture for food security, promoting health and nutrition-driven agriculture, exploring economic opportunities and addressing social challenges, and integrating one health and modern agriculture. We emphasise the critical importance of interdisciplinary and multidisciplinary research that integrates both basic and applied sciences and bridges the gaps among various stakeholders for achieving sustainable agriculture. Key points Growing demand and resource limitations pose a critical challenge for agriculture, necessitating innovative and sustainable approaches. The paper identifies 100 priority questions for the future of agriculture, indicating current and future research directions. Sustainable agriculture depends on interdisciplinary and multidisciplinary research that harmonises basic and applied sciences and fosters collaboration among different stakeholders