PUBLICATION
TAMM41 is required for heart valve differentiation via regulation of PINK-PARK2 dependent mitophagy
- Authors
- Yang, R.M., Tao, J., Zhan, M., Yuan, H., Wang, H.H., Chen, S.J., Zhu, C., de Thé, H., Zhou, J., Guo, Y., Zhu, J.
- ID
- ZDB-PUB-190303-7
- Date
- 2019
- Source
- Cell death and differentiation 26(11): 2430-2446 (Journal)
- Registered Authors
- Chen, Zhu, Zhu, Jun
- Keywords
- none
- MeSH Terms
-
- Adolescent
- Animals
- Animals, Genetically Modified
- Cell Differentiation
- Cell Line
- Child
- Child, Preschool
- Female
- Heart Valves/embryology*
- Humans
- Male
- Mitochondria/metabolism*
- Mitochondrial Proteins/metabolism
- Mitophagy/physiology*
- Myocytes, Cardiac/pathology
- Plasma Membrane Calcium-Transporting ATPases/metabolism
- Protein Serine-Threonine Kinases/metabolism*
- Ubiquitin-Protein Ligases/metabolism*
- Young Adult
- Zebrafish/embryology
- PubMed
- 30824836 Full text @ Cell Death Differ.
Citation
Yang, R.M., Tao, J., Zhan, M., Yuan, H., Wang, H.H., Chen, S.J., Zhu, C., de Thé, H., Zhou, J., Guo, Y., Zhu, J. (2019) TAMM41 is required for heart valve differentiation via regulation of PINK-PARK2 dependent mitophagy. Cell death and differentiation. 26(11):2430-2446.
Abstract
TAMM41, located within the congenital heart diseases (CHD) sensitive region of 3p25 deletion syndrome, is a mitochondrial membrane maintenance protein critical for yeast survival, but its function in higher vertebrates remains unknown. Via in vivo zebrafish model, we found that tamm41 is highly expressed in the developing heart and deficiency of which led to heart valve abnormalities. Molecular mechanistic studies revealed that TAMM41 interacts and modulates the PINK1-PARK2 dependent mitophagy pathway, thereby implicating TAMM41 in heart valve development during zebrafish embryonic cardiogenesis. Furthermore, through screening of the congenital heart diseases (CHD) sensitive region of 3p25 deletion syndrome among 118 sporadic atrioventricular septal defect (AVSD) patients, we identified three cases carrying heterozygous pathogenic intronic variants of TAMM41. All three cases lacked normal full-length TAMM41 transcripts, most likely due to specific expression of the mutant allele. Collectively, our studies highlight essential roles for TAMM41-dependent mitophagy in development of the heart and provide novel insights into the etiology of AVSD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping