Unknown

Dataset Information

0

TAMM41 is required for heart valve differentiation via regulation of PINK-PARK2 dependent mitophagy.


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.

SUBMITTER: Yang RM 

PROVIDER: S-EPMC6888875 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

TAMM41 is required for heart valve differentiation via regulation of PINK-PARK2 dependent mitophagy.

Yang Rui Meng RM   Tao Jiong J   Zhan Ming M   Yuan Hao H   Wang Hai Hong HH   Chen Sai Juan SJ   Chen Zhu Z   de Thé Hugues H   Zhou Jun J   Guo Ying Y   Zhu Jun J  

Cell death and differentiation 20190301 11


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 p  ...[more]

Similar Datasets

| S-EPMC4502823 | biostudies-other
| S-EPMC6314648 | biostudies-literature
| S-EPMC4502689 | biostudies-literature
| S-EPMC4590680 | biostudies-literature
| S-EPMC7212530 | biostudies-literature
| S-EPMC4876055 | biostudies-literature
| S-EPMC6834391 | biostudies-literature
| S-EPMC7475663 | biostudies-literature
| S-EPMC5361599 | biostudies-literature
| S-EPMC5240832 | biostudies-literature