Cargando…
Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility
Sirtuin1 (SIRT1) and Sirtuin3 (SIRT3) protects cardiac function against ischemia/reperfusion (I/R) injury. Mitochondria are critical in response to myocardial I/R injury as disturbance of mitochondrial dynamics contributes to cardiac dysfunction. It is hypothesized that SIRT1 and SIRT3 are critical...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282250/ https://www.ncbi.nlm.nih.gov/pubmed/34216536 http://dx.doi.org/10.1111/acel.13419 |
_version_ | 1783722977139884032 |
---|---|
author | Zhang, Jingwen He, Zhibin Fedorova, Julia Logan, Cole Bates, Lauryn Davitt, Kayla Le, Van Murphy, Jiayuan Li, Melissa Wang, Mingyi Lakatta, Edward G. Ren, Di Li, Ji |
author_facet | Zhang, Jingwen He, Zhibin Fedorova, Julia Logan, Cole Bates, Lauryn Davitt, Kayla Le, Van Murphy, Jiayuan Li, Melissa Wang, Mingyi Lakatta, Edward G. Ren, Di Li, Ji |
author_sort | Zhang, Jingwen |
collection | PubMed |
description | Sirtuin1 (SIRT1) and Sirtuin3 (SIRT3) protects cardiac function against ischemia/reperfusion (I/R) injury. Mitochondria are critical in response to myocardial I/R injury as disturbance of mitochondrial dynamics contributes to cardiac dysfunction. It is hypothesized that SIRT1 and SIRT3 are critical components to maintaining mitochondria homeostasis especially mitochondrial dynamics to exert cardioprotective actions under I/R stress. The results demonstrated that deficiency of SIRT1 and SIRT3 in aged (24–26 months) mice hearts led to the exacerbated cardiac dysfunction in terms of cardiac systolic dysfunction, cardiomyocytes contractile defection, and abnormal cardiomyocyte calcium flux during I/R stress. Moreover, the deletion of SIRT1 or SIRT3 in young (4–6 months) mice hearts impair cardiomyocyte contractility and shows aging‐like cardiac dysfunction upon I/R stress, indicating the crucial role of SIRT1 and SIRT3 in protecting myocardial contractility from I/R injury. The biochemical and seahorse analysis showed that the deficiency of SIRT1/SIRT3 leads to the inactivation of AMPK and alterations in mitochondrial oxidative phosphorylation (OXPHOS) that causes impaired mitochondrial respiration in response to I/R stress. Furthermore, the remodeling of the mitochondria network goes together with hypoxic stress, and mitochondria undergo the processes of fusion with the increasing elongated branches during hypoxia. The transmission electron microscope data showed that cardiac SIRT1/SIRT3 deficiency in aging alters mitochondrial morphology characterized by the impairment of mitochondria fusion under I/R stress. Thus, the age‐related deficiency of SIRT1/SIRT3 in the heart affects mitochondrial dynamics and respiration function that resulting in the impaired contractile function of cardiomyocytes in response to I/R. |
format | Online Article Text |
id | pubmed-8282250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82822502021-07-16 Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility Zhang, Jingwen He, Zhibin Fedorova, Julia Logan, Cole Bates, Lauryn Davitt, Kayla Le, Van Murphy, Jiayuan Li, Melissa Wang, Mingyi Lakatta, Edward G. Ren, Di Li, Ji Aging Cell Original Articles Sirtuin1 (SIRT1) and Sirtuin3 (SIRT3) protects cardiac function against ischemia/reperfusion (I/R) injury. Mitochondria are critical in response to myocardial I/R injury as disturbance of mitochondrial dynamics contributes to cardiac dysfunction. It is hypothesized that SIRT1 and SIRT3 are critical components to maintaining mitochondria homeostasis especially mitochondrial dynamics to exert cardioprotective actions under I/R stress. The results demonstrated that deficiency of SIRT1 and SIRT3 in aged (24–26 months) mice hearts led to the exacerbated cardiac dysfunction in terms of cardiac systolic dysfunction, cardiomyocytes contractile defection, and abnormal cardiomyocyte calcium flux during I/R stress. Moreover, the deletion of SIRT1 or SIRT3 in young (4–6 months) mice hearts impair cardiomyocyte contractility and shows aging‐like cardiac dysfunction upon I/R stress, indicating the crucial role of SIRT1 and SIRT3 in protecting myocardial contractility from I/R injury. The biochemical and seahorse analysis showed that the deficiency of SIRT1/SIRT3 leads to the inactivation of AMPK and alterations in mitochondrial oxidative phosphorylation (OXPHOS) that causes impaired mitochondrial respiration in response to I/R stress. Furthermore, the remodeling of the mitochondria network goes together with hypoxic stress, and mitochondria undergo the processes of fusion with the increasing elongated branches during hypoxia. The transmission electron microscope data showed that cardiac SIRT1/SIRT3 deficiency in aging alters mitochondrial morphology characterized by the impairment of mitochondria fusion under I/R stress. Thus, the age‐related deficiency of SIRT1/SIRT3 in the heart affects mitochondrial dynamics and respiration function that resulting in the impaired contractile function of cardiomyocytes in response to I/R. John Wiley and Sons Inc. 2021-07-03 2021-07 /pmc/articles/PMC8282250/ /pubmed/34216536 http://dx.doi.org/10.1111/acel.13419 Text en © 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zhang, Jingwen He, Zhibin Fedorova, Julia Logan, Cole Bates, Lauryn Davitt, Kayla Le, Van Murphy, Jiayuan Li, Melissa Wang, Mingyi Lakatta, Edward G. Ren, Di Li, Ji Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility |
title | Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility |
title_full | Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility |
title_fullStr | Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility |
title_full_unstemmed | Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility |
title_short | Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility |
title_sort | alterations in mitochondrial dynamics with age‐related sirtuin1/sirtuin3 deficiency impair cardiomyocyte contractility |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282250/ https://www.ncbi.nlm.nih.gov/pubmed/34216536 http://dx.doi.org/10.1111/acel.13419 |
work_keys_str_mv | AT zhangjingwen alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT hezhibin alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT fedorovajulia alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT logancole alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT bateslauryn alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT davittkayla alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT levan alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT murphyjiayuan alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT limelissa alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT wangmingyi alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT lakattaedwardg alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT rendi alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility AT liji alterationsinmitochondrialdynamicswithagerelatedsirtuin1sirtuin3deficiencyimpaircardiomyocytecontractility |