The role of circadian clock-controlled mitochondrial dynamics in diabetic cardiomyopathy

Abstract

Diabetes mellitus is a metabolic disease with a high prevalence worldwide, and cardiovascular complications are the leading cause of mortality in patients with diabetes. Diabetic cardiomyopathy (DCM), which is prone to heart failure with preserved ejection fraction, is defined as a cardiac dysfunction without conventional cardiac risk factors such as coronary heart disease and hypertension. Mitochondria are the centers of energy metabolism that are very important for maintaining the function of the heart. They are highly dynamic in response to environmental changes through mitochondrial dynamics. The disruption of mitochondrial dynamics is closely related to the occurrence and development of DCM. Mitochondrial dynamics are controlled by circadian clock and show oscillation rhythm. This rhythm enables mitochondria to respond to changing energy demands in different environments, but it is disordered in diabetes. In this review, we summarize the significant role of circadian clock-controlled mitochondrial dynamics in the etiology of DCM and hope to play a certain enlightening role in the treatment of DCM.

Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses

“…Do other mitochondria located receptors linked to the melatonergic pathway, such as TrkB, AhR and α7nAChR modulate the capacity of “batteries” to be synchronized? Mitochondrial dynamics are powerfully regulated by the circadian clock, showing a metabolic oscillatory rhythm [ 198 ], indicating a significant role for pineal melatonin modulation of circadian genes as well as sirtuin-1 and sirtuin-3, which are intimately involved in regulating the metabolic circadian rhythm [ 198 ]. As to how CAR and the GR translocation to mitochondria interface with this will be important to determine, especially as disordered cristae on the inner mitochondrial membrane increase superoxide production [ 199 ].…”

Mitochondrial Dynamics in Pulmonary Hypertension

“…New drugs that have emerged targeting mitochondrial dynamics controlled by the clock have brought hope for therapeutic improvements. The first drug based on the circadian clock was melatonin, a hormone secreted by the pineal gland [70]. Exogenous melatonin supplementation increased myocardial ROR levels through the reduction of dysfunctional mitochondria, ER stress, myocardial apoptosis, autophagy dysfunction, and oxidative stress damage [70,71].…”

“…Furthermore, in recent years new therapeutic alternatives have been presented, such as nobiletin, CRY activator (KL001), Rev-ERB-α/β agonist (especially SR9011/SR9009), among other small molecule chemical enhancers targeted at the circadian system. These chemical compounds restored cardiac circadian rhythms and oscillatory patterns of metabolic gene expression, resulting in phenotypic improvements in insulin resistance, lipotoxicity, oxidative stress, and dysfunctional mitochondrial dynamics [70,72,73]. Therefore, interventions involving the circadian clock and mitochondrial dynamics are promising therapeutic approaches.…”