FUNDC1: A Promising Mitophagy Regulator at the Mitochondria-Associated Membrane for Cardiovascular Diseases

Abstract

Mitochondrial autophagy (or mitophagy) regulates the mitochondrial network and function to contribute to multiple cellular processes. The protective effect of homeostatic mitophagy in cardiovascular diseases (CVDs) has attracted increasing attention. FUN14 domain containing 1 (FUNDC1), an identified mitophagy receptor, plays an essential role in CVDs. Different expression levels of FUNDC1 and its phosphorylated state at different sites alleviate or exacerbate hypoxia and ischemia/reperfusion injury, cardiac hypertrophy, or metabolic damage through promotion or inhibition of mitophagy. In addition, FUNDC1 can be enriched at contact sites between mitochondria and the endoplasmic reticulum (ER), determining the formation of mitochondria-associated membranes (MAMs) that regulate cellular calcium (Ca2+) homeostasis and mitochondrial dynamics to prevent heart dysfunction. Moreover, FUNDC1 has also been involved in inflammatory cardiac diseases such as septic cardiomyopathy. In this review, we collect and summarize the evidence on the roles of FUNDC1 exclusively in various CVDs, describing its interactions with different cellular organelles, its involvement in multiple cellular processes, and its associated signaling pathways. FUNDC1 may become a promising therapeutic target for the prevention and management of various CVDs.

Impact of Sodium–Glucose Cotransporter 2 (SGLT2) Inhibitors on Arterial Stiffness and Vascular Aging—What Do We Know So Far? (A Narrative Review)

“…Most clinical studies documented canagliflozin as the only SGLT2 inhibitor that activates AMP-activated protein kinase (AMPK) [ 131 ] and inhibits pro-inflammatory status by decreasing the concentration of chemokines and cytokines without interfering with IL-1β signaling pathways [ 132 ]. In a recent study, Cai et al [ 133 ] emphasized the protective role of empagliflozin in mitochondrial metabolism through the activation of the AMPKα1/UNC-51-like kinase (ULK1)/FUN14 domain containing 1 (FUNDC1)/mitophagy pathway both in intro and in vivo [ 134 , 135 , 136 ]. In addition to acting at the level of mitochondrial metabolism, empagliflozin alleviates microvascular dysfunction by mediating the interaction between cardiac microvascular endothelial cells and cardiac myocytes [ 137 , 138 ].…”

Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

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