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Cisd2 is essential to delaying cardiac aging and to maintaining heart functions.
- Source :
-
PLoS biology [PLoS Biol] 2019 Oct 08; Vol. 17 (10), pp. e3000508. Date of Electronic Publication: 2019 Oct 08 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- CDGSH iron-sulfur domain-containing protein 2 (Cisd2) is pivotal to mitochondrial integrity and intracellular Ca2+ homeostasis. In the heart of Cisd2 knockout mice, Cisd2 deficiency causes intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Furthermore, Cisd2 deficiency disrupts Ca2+ homeostasis via dysregulation of sarco/endoplasmic reticulum Ca2+-ATPase (Serca2a) activity, resulting in an increased level of basal cytosolic Ca2+ and mitochondrial Ca2+ overload in cardiomyocytes. Most strikingly, in Cisd2 transgenic mice, a persistently high level of Cisd2 is sufficient to delay cardiac aging and attenuate age-related structural defects and functional decline. In addition, it results in a younger cardiac transcriptome pattern during old age. Our findings indicate that Cisd2 plays an essential role in cardiac aging and in the heart's electromechanical functioning. They highlight Cisd2 as a novel drug target when developing therapies to delay cardiac aging and ameliorate age-related cardiac dysfunction.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Aging, Premature metabolism
Aging, Premature physiopathology
Animals
Atrioventricular Block diagnostic imaging
Atrioventricular Block metabolism
Atrioventricular Block physiopathology
Autophagy-Related Proteins deficiency
Calcium metabolism
Electrocardiography
Gene Expression Profiling
Gene Expression Regulation
Heart physiology
Homeostasis physiology
Male
Mice
Mice, Knockout
Mitochondria, Heart genetics
Mitochondria, Heart metabolism
Myocytes, Cardiac cytology
Myocytes, Cardiac physiology
Nerve Tissue Proteins deficiency
Sarcomeres physiology
Sarcoplasmic Reticulum Calcium-Transporting ATPases metabolism
Transcriptome
Aging physiology
Aging, Premature genetics
Atrioventricular Block genetics
Autophagy-Related Proteins genetics
Heart physiopathology
Nerve Tissue Proteins genetics
Sarcoplasmic Reticulum Calcium-Transporting ATPases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1545-7885
- Volume :
- 17
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PLoS biology
- Publication Type :
- Academic Journal
- Accession number :
- 31593566
- Full Text :
- https://doi.org/10.1371/journal.pbio.3000508