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Mitochondrial Arrest on the Microtubule Highway—A Feature of Heart Failure and Diabetic Cardiomyopathy?
- Source :
- Frontiers in Cardiovascular Medicine, Frontiers in Cardiovascular Medicine, Vol 8 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- A pathophysiological consequence of both type 1 and 2 diabetes is remodelling of the myocardium leading to the loss of left ventricular pump function and ultimately heart failure (HF). Abnormal cardiac bioenergetics associated with mitochondrial dysfunction occurs in the early stages of HF. Key factors influencing mitochondrial function are the shape, size and organisation of mitochondria within cardiomyocytes, with reports identifying small, fragmented mitochondria in the myocardium of diabetic patients. Cardiac mitochondria are now known to be dynamic organelles (with various functions beyond energy production); however, the mechanisms that underpin their dynamism are complex and links to motility are yet to be fully understood, particularly within the context of HF. This review will consider how the outer mitochondrial membrane protein Miro1 (Rhot1) mediates mitochondrial movement along microtubules via crosstalk with kinesin motors and explore the evidence for molecular level changes in the setting of diabetic cardiomyopathy. As HF and diabetes are recognised inflammatory conditions, with reports of enhanced activation of the NLRP3 inflammasome, we will also consider evidence linking microtubule organisation, inflammation and the association to mitochondrial motility. Diabetes is a global pandemic but with limited treatment options for diabetic cardiomyopathy, therefore we also discuss potential therapeutic approaches to target the mitochondrial-microtubule-inflammatory axis.
- Subjects :
- 0301 basic medicine
Mini Review
heart failure
Context (language use)
Cardiovascular Medicine
Mitochondrion
microtubules
03 medical and health sciences
0302 clinical medicine
NLRP3
Diabetic cardiomyopathy
Diabetes mellitus
mitochondrial dysfunction
diabetic cardiomyopathy
medicine
Diseases of the circulatory (Cardiovascular) system
business.industry
Inflammasome
mitochondrial movement
HDAC6
medicine.disease
Cell biology
Crosstalk (biology)
030104 developmental biology
Miro1
RC666-701
Heart failure
Kinesin
Cardiology and Cardiovascular Medicine
business
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 2297055X
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Frontiers in Cardiovascular Medicine
- Accession number :
- edsair.doi.dedup.....cac1a78c610e698a7d83420c262369ea
- Full Text :
- https://doi.org/10.3389/fcvm.2021.689101