Mitochondria and Calcium Homeostasis: Cisd2 as a Big Player in Cardiac Ageing

International Journal of Molecular Sciences

Cheng-Heng Kao¹  Chi-Hsiao Yeh²  Yi-Ju Chou³  Ting-Fen Tsai³ 

[1] Center of General Education, Chang Gung University, Taoyuan 333, Taiwan;Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linko 333, Taiwan;Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 350, Taiwan;

关键词: cardiac ageing;    Cisd2;    mitochondria-associated membranes (MAMs);    mitochondria;    calcium homeostasis;    energy flexibility;   

DOI  :  10.3390/ijms21239238

来源: DOAJ

【 摘 要 】

The ageing of human populations has become a problem throughout the world. In this context, increasing the healthy lifespan of individuals has become an important target for medical research and governments. Cardiac disease remains the leading cause of morbidity and mortality in ageing populations and results in significant increases in healthcare costs. Although clinical and basic research have revealed many novel insights into the pathways that drive heart failure, the molecular mechanisms underlying cardiac ageing and age-related cardiac dysfunction are still not fully understood. In this review we summarize the most updated publications and discuss the central components that drive cardiac ageing. The following characters of mitochondria-related dysfunction have been identified during cardiac ageing: (a) disruption of the integrity of mitochondria-associated membrane (MAM) contact sites; (b) dysregulation of energy metabolism and dynamic flexibility; (c) dyshomeostasis of Ca²⁺ control; (d) disturbance to mitochondria–lysosomal crosstalk. Furthermore, Cisd2, a pro-longevity gene, is known to be mainly located in the endoplasmic reticulum (ER), mitochondria, and MAM. The expression level of Cisd2 decreases during cardiac ageing. Remarkably, a high level of Cisd2 delays cardiac ageing and ameliorates age-related cardiac dysfunction; this occurs by maintaining correct regulation of energy metabolism and allowing dynamic control of metabolic flexibility. Together, our previous studies and new evidence provided here highlight Cisd2 as a novel target for developing therapies to promote healthy ageing

【 授权许可】

Unknown