Nordeidet Ada Nilsen, Marwarha Gurdeep S A, Røsand Øystein, Johansen Victoria, Garten Karin, Høydal Morten A, Langaas Mette, Bye Anja
Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Group of Molecular and Cellular Cardiology, Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
PLoS One. 2025 Jun 25;20(6):e0326249. doi: 10.1371/journal.pone.0326249. eCollection 2025.
Low cardiorespiratory fitness (CRF) is a well-established risk factor for cardiovascular disease (CVD) and all-cause mortality. Since CRF is largely genetically determined, understanding the genetic influences on CRF might reveal the protective mechanisms of high CRF. One gene found to be associated with CRF is COX7A2L. COX7A2L is a mitochondrial supercomplex assembly factor, but its role in cellular metabolism remains a topic of discussion. We hypothesized that COX7A2L could play a role in cellular respiration in cardiomyocytes, affecting cardiac function and CRF. To determine the effect of COX7A2L on cardiomyocyte function, we overexpressed and knocked down COX7A2L in human AC16 cardiomyocytes and performed MTT assays and Seahorse XF Cell Mito Stress Tests to assess cell viability and mitochondrial function. For the mitochondrial function measurements, we stimulated the cells with isoproterenol to investigate if the effect of altering COX7A2L levels would be larger under simulated increased energy demand. Overexpression and knockdown were validated using sandwich ELISA. Our findings showed that altering COX7A2L expression in human AC16 cardiomyocytes did not significantly affect cell viability or mitochondrial function. Further research is necessary to determine whether COX7A2L influences cardiomyocyte function and CRF.
低心肺适能（CRF）是心血管疾病（CVD）和全因死亡率公认的风险因素。由于CRF很大程度上由基因决定，了解基因对CRF的影响可能会揭示高CRF的保护机制。已发现一个与CRF相关的基因是COX7A2L。COX7A2L是一种线粒体超复合物组装因子，但其在细胞代谢中的作用仍是一个讨论话题。我们假设COX7A2L可能在心肌细胞的细胞呼吸中发挥作用，影响心脏功能和CRF。为了确定COX7A2L对心肌细胞功能的影响，我们在人AC16心肌细胞中过表达和敲低COX7A2L，并进行MTT试验和海马XF细胞线粒体应激试验以评估细胞活力和线粒体功能。对于线粒体功能测量，我们用异丙肾上腺素刺激细胞，以研究在模拟能量需求增加的情况下改变COX7A2L水平的影响是否会更大。使用夹心ELISA验证过表达和敲低。我们的研究结果表明，改变人AC16心肌细胞中COX7A2L的表达不会显著影响细胞活力或线粒体功能。需要进一步研究以确定COX7A2L是否影响心肌细胞功能和CRF。
