Mitochondrial Arrest on the Microtubule Highway—A Feature of Heart Failure and Diabetic Cardiomyopathy?

Frontiers in Cardiovascular Medicine

article

Sarah Kassab¹  Zainab Albalawi¹  Hussam Daghistani¹  Ashraf Kitmitto¹ 

[1] Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, Manchester Academic Health Science Centre, The University of Manchester

关键词: diabetic cardiomyopathy;    heart failure;    Miro1;    microtubules;    HDAC6;    NLRP3;    mitochondrial dysfunction;    mitochondrial movement;   

DOI  :  10.3389/fcvm.2021.689101

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY