Matches in SemOpenAlex for { <https://semopenalex.org/work/W2917377730> ?p ?o ?g. }
- W2917377730 abstract "Abstract Protein quality control is pivotal to cellular homeostasis and integrity of cardiomyocytes for maintenance of normal heart function. The unfolded protein response (UPR) is an adaptive process to modulate protein quality control in the endoplasmic reticulum (ER) and mitochondria, and is accordingly termed UPR ER and UPR mt , respectively. Lon protease (LonP1) is a highly conserved mitochondrial protease to modulate UPR mt , which is involved in regulating metabolism, mitophagy, and stress response. However, whether LonP1 regulates UPR ER remains elusive. To investigate the regulation of protein quality control in cardiomyocytes, we generated cardiac-specific LonP1 deletion mice. Our findings show that LonP1 deficiency caused impaired mitochondrial respiratory function and fragmentation. Surprisingly, both UPR ER and UPR mt is substantially induced in LonP1-deletion heart suggesting of LonP1 as a novel regulator of UPR ER ; however, the activation of UPR ER occurs earlier than UPR mt in response to LonP1 deletion. Consequently, cardiac-specific LonP1 deficiency causes aberrant metabolic reprogramming of cardiomyocytes, pathological heart remodeling, as well as impeded heart function. Thus, we uncovered the novel function of LonP1 as an UPR mt mediator, and reciprocal orchestration of UPR mt and UPR ER and mitochondrial dynamics regulated by LonP1 in the cardiomyocytes that is critical to maintain heart function, which offers exciting new insights into the potential therapeutic strategy for heart failure." @default.
- W2917377730 created "2019-03-02" @default.
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- W2917377730 date "2019-03-01" @default.
- W2917377730 modified "2023-09-26" @default.
- W2917377730 title "LonP1 Orchestrates UPR<sup>mt</sup>and UPR<sup>ER</sup>and Mitochondrial Dynamics to Regulate Heart Function" @default.
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- W2917377730 doi "https://doi.org/10.1101/564492" @default.
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