The role of the mitochondrial protein dimer CHCHD2/10 in health and disease

骨骼肌、心脏和大脑是需要高能量的组织，受到线粒体的严重影响 功能障碍。最近，一种影响线粒体的新形式的遗传病被认为与 线粒体蛋白CHCHD10(D10)的突变，其功能在很大程度上仍不清楚。突变体D10 引起严重的常染色体显性遗传性线粒体疾病，具有不同的表型特征，范围从 从肌病、心肌病到运动神经元病、额颞叶痴呆。父R01，即 与这项多样性补充申请相关联的是研究D10的正常功能和机制 D10 S55L突变小鼠潜在的线粒体改变。该补编将为女士的工作提供支持。 曼弗雷迪博士团队神经科学项目的研究生Nneka Southwell说道。这次会议的重点是 附录中建议的研究是关于涉及1C代谢和核苷酸的代谢重排 她在D10 S55L突变小鼠身上观察到的不平衡，从受影响最严重的组织开始， 心脏，但也探索新陈代谢的变化在不同的大脑区域。后者具有很高的创新性，因为 对中枢神经系统中的线粒体代谢应激反应知之甚少，可能有一些 途径与心脏和其他组织共享，而其他途径可能完全不同。不适应代谢 重新连接是一个新兴和迷人的领域，它具有提供新的疾病生物标志物的令人兴奋的前景。 和治疗目标，不仅针对这种线粒体疾病，也针对许多其他相同的疾病 代谢适应机制。为本多样性副刊提出的研究将提供充足的 索思韦尔女士有机会成为新陈代谢和疾病专家，这是一个研究领域 在生物医学领域获得了巨大的动力，因为代谢失调的作用越来越大 与一系列疾病有关。她将积累的知识和技能 在这个项目上的工作将使她能够更好地发展她独立的、前沿的研究 论代谢功能障碍在退行性疾病中的作用。

Skeletal muscle, heart, and brain are high-energy requiring tissues that are severely affected by mitochondrial dysfunction. Recently a novel form of genetic disease affecting mitochondria has been associated with mutations in a mitochondrial protein, CHCHD10 (D10), whose function is still largely unknown. Mutant D10 causes severe autosomal dominant mitochondrial diseases, with diverse phenotypic features, ranging from myopathy and cardiomyopathy to motor neuron disease and frontotemporal dementia. The parent R01 that is linked to this application for Diversity Supplement investigates the normal function of D10 and the mechanisms underlying mitochondrial alterations in D10 S55L mutant mice. The supplement will support the work of Ms. Nneka Southwell, a graduate student in the Neuroscience Program in Dr. Manfredi’s group. The focus of the studies proposed in the supplement is on the metabolic rewiring involving 1C metabolism and nucleotide imbalance, which she has observed in the D10 S55L mutant mouse, starting from the most affected tissue, the heart, but also exploring metabolic alterations in various brain regions. The latter is highly innovative because very little is known about mitochondrial metabolic stress responses in the CNS and it is possible that some pathways are shared with heart and other tissues, while other could differ entirely. Maladaptive metabolic rewiring is an emerging and fascinating field, which holds exciting promise to provide novel disease biomarkers and therapeutic targets, not only for this mitochondrial disorder, but also for many other diseases that share metabolic adaptation mechanisms. The studies proposed for this Diversity Supplement will provide ample opportunities for Ms. Southwell to become an expert in metabolism and disease, an area of research that is gaining tremendous momentum in the biomedical space, as a role for metabolic dysregulation is increasingly being linked to a broad spectrum of diseases. The knowledge and technical skills that she will accumulate working on this project will position her well to being able to develop her independent, cutting-edge research on the role of metabolic dysfunction in degenerative diseases.