PUBLICATION

Tom70 serves as a molecular switch to determine pathological cardiac hypertrophy

Authors

Li, J., Qi, M., Li, C., Shi, D., Zhang, D., Xie, D., Yuan, T., Feng, J., Liu, Y., Liang, D., Xu, X., Chen, J., Xu, L., Zhang, H., Ye, J., Lv, F., Huang, J., Peng, L., Chen, Y.H.

ID

ZDB-PUB-170214-312

Date

2014

Source

Cell Research 24: 977-93 (Journal)

Registered Authors

Huang, Jian, Li, Jun

Keywords

none

MeSH Terms

Cardiomegaly/metabolism
Cardiomegaly/pathology*
Mitochondrial Membrane Transport Proteins/antagonists & inhibitors
Mitochondrial Membrane Transport Proteins/genetics
Mitochondrial Membrane Transport Proteins/metabolism*
RNA, Small Interfering/metabolism
Zebrafish/metabolism
Rats
Down-Regulation
Oxidative Stress
Animals
Heart Failure/metabolism
Heart Failure/pathology
Mice, Inbred C57BL
Rats, Sprague-Dawley
Myocytes, Cardiac/cytology
Myocytes, Cardiac/metabolism
Disease Models, Animal
Male
RNA Interference
Humans
Mice

(all 22)

PubMed

25022898 Full text @ Cell Res.

Abstract

Pathological cardiac hypertrophy is an inevitable forerunner of heart failure. Regardless of the etiology of cardiac hypertrophy, cardiomyocyte mitochondrial alterations are always observed in this context. The translocases of mitochondrial outer membrane (Tom) complex governs the import of mitochondrial precursor proteins to maintain mitochondrial function under pathophysiological conditions; however, its role in the development of pathological cardiac hypertrophy remains unclear. Here, we showed that Tom70 was downregulated in pathological hypertrophic hearts from humans and experimental animals. The reduction in Tom70 expression produced distinct pathological cardiomyocyte hypertrophy both in vivo and in vitro. The defective mitochondrial import of Tom70-targeted optic atrophy-1 triggered intracellular oxidative stress, which led to a pathological cellular response. Importantly, increased Tom70 levels provided cardiomyocytes with full resistance to diverse pro-hypertrophic insults. Together, these results reveal that Tom70 acts as a molecular switch that orchestrates hypertrophic stresses and mitochondrial responses to determine pathological cardiac hypertrophy.

Genes / Markers

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-opa1	standard conditions	Long-pec	cardiac muscle cell increased size, abnormal	Fig. 6
WT + MO1-opa1	standard conditions	Day 5	whole organism opa1 expression decreased amount, abnormal	Fig. 6
WT + MO1-tomm70a	standard conditions	Long-pec	cardiac muscle cell increased size, abnormal	Fig. 4
WT + MO1-tomm70a	standard conditions	Long-pec	heart contraction decreased process quality, abnormal	Fig. 4
WT + MO1-tomm70a	standard conditions	Long-pec	reactive oxygen species metabolic process increased occurrence, abnormal	Fig. 5
WT + MO1-tomm70a	standard conditions	Long-pec	whole organism tomm70a expression decreased amount, abnormal	Fig. 4
WT + MO1-tomm70a	standard conditions	Long-pec	whole organism Ab1-tomm70 labeling decreased amount, abnormal	Fig. 4
WT + MO1-tomm70a	standard conditions	Day 5	cardiac muscle cell mitochondrion morphology, abnormal	Fig. 6
WT + MO1-tomm70a	standard conditions	Day 5	cardiac ventricle constricted, abnormal	Fig. 4
WT + MO1-tomm70a	standard conditions	Day 5	heart hypertrophic, abnormal	Fig. 4

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Li et al., 2014 ZDB-PUB-170214-312 PMID:25022898

Tom70 serves as a molecular switch to determine pathological cardiac hypertrophy

Li et al., 2014

ZDB-PUB-170214-312
PMID:25022898