Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-117 |
Sentence |
denotes |
The nuclear receptor RORα preserves cardiomyocyte mitochondrial function by regulating caveolin-3-mediated mitophagy. |
T2 |
118-231 |
Sentence |
denotes |
Preserving optimal mitochondrial function is critical in the heart, which is the most ATP-avid organ in the body. |
T3 |
232-437 |
Sentence |
denotes |
Recently, we showed that global deficiency of the nuclear receptor RORα in the "staggerer" mouse exacerbates angiotensin II-induced cardiac hypertrophy and compromises cardiomyocyte mitochondrial function. |
T4 |
438-525 |
Sentence |
denotes |
However, the mechanisms underlying these observations have not been defined previously. |
T5 |
526-709 |
Sentence |
denotes |
Here, we used pharmacological and genetic gain- and loss-of-function tools to demonstrate that RORα regulates cardiomyocyte mitophagy to preserve mitochondrial abundance and function. |
T6 |
710-880 |
Sentence |
denotes |
We found that cardiomyocyte mitochondria in staggerer mice with lack of functional RORα were less numerous and exhibited fewer mitophagy events than those in WT controls. |
T7 |
881-1098 |
Sentence |
denotes |
The hearts of our novel cardiomyocyte-specific RORα KO mouse line demonstrated impaired contractile function, enhanced oxidative stress, increased apoptosis, and reduced autophagic flux relative to Cre(-) littermates. |
T8 |
1099-1251 |
Sentence |
denotes |
We found that cardiomyocyte mitochondria in "staggerer" mice with lack of functional RORα were upregulated by hypoxia, a classical inducer of mitophagy. |
T9 |
1252-1390 |
Sentence |
denotes |
The loss of RORα blunted mitophagy and broadly compromised mitochondrial function in normoxic and hypoxic conditions in vivo and in vitro. |
T10 |
1391-1598 |
Sentence |
denotes |
We also show that RORα is a direct transcriptional regulator of the mitophagy mediator caveolin-3 in cardiomyocytes and that enhanced expression of RORα increases caveolin-3 abundance and enhances mitophagy. |
T11 |
1599-1782 |
Sentence |
denotes |
Finally, knockdown of RORα impairs cardiomyocyte mitophagy, compromises mitochondrial function, and induces apoptosis, but these defects could be rescued by caveolin-3 overexpression. |
T12 |
1783-1991 |
Sentence |
denotes |
Collectively, these findings reveal a novel role for RORα in regulating mitophagy through caveolin-3 and expand our currently limited understanding of the mechanisms underlying RORα-mediated cardioprotection. |
T1 |
0-117 |
Sentence |
denotes |
The nuclear receptor RORα preserves cardiomyocyte mitochondrial function by regulating caveolin-3-mediated mitophagy. |
T2 |
118-231 |
Sentence |
denotes |
Preserving optimal mitochondrial function is critical in the heart, which is the most ATP-avid organ in the body. |
T3 |
232-437 |
Sentence |
denotes |
Recently, we showed that global deficiency of the nuclear receptor RORα in the "staggerer" mouse exacerbates angiotensin II-induced cardiac hypertrophy and compromises cardiomyocyte mitochondrial function. |
T4 |
438-525 |
Sentence |
denotes |
However, the mechanisms underlying these observations have not been defined previously. |
T5 |
526-709 |
Sentence |
denotes |
Here, we used pharmacological and genetic gain- and loss-of-function tools to demonstrate that RORα regulates cardiomyocyte mitophagy to preserve mitochondrial abundance and function. |
T6 |
710-880 |
Sentence |
denotes |
We found that cardiomyocyte mitochondria in staggerer mice with lack of functional RORα were less numerous and exhibited fewer mitophagy events than those in WT controls. |
T7 |
881-1098 |
Sentence |
denotes |
The hearts of our novel cardiomyocyte-specific RORα KO mouse line demonstrated impaired contractile function, enhanced oxidative stress, increased apoptosis, and reduced autophagic flux relative to Cre(-) littermates. |
T8 |
1099-1251 |
Sentence |
denotes |
We found that cardiomyocyte mitochondria in "staggerer" mice with lack of functional RORα were upregulated by hypoxia, a classical inducer of mitophagy. |
T9 |
1252-1390 |
Sentence |
denotes |
The loss of RORα blunted mitophagy and broadly compromised mitochondrial function in normoxic and hypoxic conditions in vivo and in vitro. |
T10 |
1391-1598 |
Sentence |
denotes |
We also show that RORα is a direct transcriptional regulator of the mitophagy mediator caveolin-3 in cardiomyocytes and that enhanced expression of RORα increases caveolin-3 abundance and enhances mitophagy. |
T11 |
1599-1782 |
Sentence |
denotes |
Finally, knockdown of RORα impairs cardiomyocyte mitophagy, compromises mitochondrial function, and induces apoptosis, but these defects could be rescued by caveolin-3 overexpression. |
T12 |
1783-1991 |
Sentence |
denotes |
Collectively, these findings reveal a novel role for RORα in regulating mitophagy through caveolin-3 and expand our currently limited understanding of the mechanisms underlying RORα-mediated cardioprotection. |