Current Opinion in Physiology最新文献

Cardiac fibrosis is an important pathological process leading to heart failure, characterized by the deposition of extracellular matrix proteins in the myocardial interstitium disrupting the normal structure and function of the myocardium. In this review, we summarized the underlying mechanisms by which exercise can exert cardioprotective effects by inhibiting cardiac fibrosis. In general, this review discussed that exercise promotes the secretion of cardioprotective exerkines, inhibits systemic activation of the renin–angiotensin system axis and sympathetic overactivation, attenuates oxidative stress and inflammatory responses, and regulates metabolism and noncoding RNA. In conclusion, our review may provide a current understanding of the mechanisms by which exercise acts as an important nonpharmacological strategy to intervene in cardiac fibrosis for cardioprotection.

Vascular aging, characterized by vascular wall thickening, collagen deposition, arterial stiffening, and endothelial dysfunction, is not necessarily determined chronologically, but can increase faster due to physical inactivity and other health risk factors. Astronauts exposed to microgravity and radiation during spaceflight undergo physiological changes associated with decrements in metabolic regulation, insulin signaling, endothelial homeostasis, and redox balance, which may foster aging features in the vasculature. Exercise has been proved an effective approach to mitigate microgravity-induced aging changes and thus protect vascular health. We here briefly review the mechanisms contributing to vascular aging changes in microgravity and exercise-afforded vasoprotection. Deep planetary exploration and longer space travel would impose unknown health risks, therefore, better understanding of exercise-induced health effects from an integrative perspective will help develop more efficient and effective exercise countermeasures.

Mitochondria are vitally important organelles within our cells. In addition to being the key energy provider, they perform numerous other essential roles ranging from calcium homeostasis to iron metabolism. Therefore, these mitochondrial functions are dependent on the quality and number of mitochondria, which needs to be dynamic in response to a cell’s changing needs. Mitochondrial numbers themselves are controlled by mitochondrial biogenesis and turnover. Multiple pathways exist that result in the turnover of mitochondria, but the focus of this review will be on mitophagy (the autophagy of mitochondria). Here, we will touch on the basic mechanisms of mitophagy and how this has been translated from cell-based studies to complex mammalian systems. We will then examine the tasks that mitophagy serves in vivo. While mitochondrial quality control is a critical function of mitophagy, we will also discuss the recent roles that mitophagy plays in metabolic remodeling.

A fraction of the cellular proteome can be selectively targeted to lysosomes for degradation within this organelle by a process known as chaperone-mediated autophagy (CMA). A dedicated network of genes and their protein products contribute to CMA execution and regulation. Here, we describe the most recent advances on the molecular dissection of CMA and on the understanding of the lysosomal and cellular components that contribute to its regulation, both under physiological conditions and in response to different stressors. The recent development of experimental mouse models to track, upregulate, or downregulate CMA in vivo has helped identify that, besides the role of CMA in cellular protein quality control, this type of autophagy also contributes to timely remodeling of the cellular functional proteome to modulate a variety of cellular processes. We review some of the novel regulatory roles of CMA and the consequences of CMA failure on physiology and cellular functioning.

Autophagy is an important cellular homoeostatic process that transports cytoplasmic constituents to lysosomes and participates in various physiological processes. Recent findings have revealed novel functional roles of autophagy in the reproductive process, and dysfunctional autophagy has been reported to be associated with male and female infertility. In this review, we summarise the recent progress regarding autophagy in fertility and discuss important concerns in this field.

Although endothelial cell (EC) dysfunction contributes to the etiology of more diseases than any other tissue in the body, EC metabolism is an understudied therapeutic target. Evidence regarding the important role of autophagy in maintaining EC homeostasis is accumulating rapidly. Here, we focus on advances over the past two years regarding how EC autophagy mediates EC nitric oxide generation in the context of aging and cardiovascular complications, including coronary artery disease, aneurysm, and stroke. In addition, insight concerning the efficacy of maneuvers designed to boost EC autophagy in an effort to combat cardiovascular complications associated with repressed EC autophagy is discussed.

Since the initial discovery of autophagy in rat liver over 60 years ago, studies on hepatic autophagy have provided insight into the mechanisms and physiological functions of autophagy. These findings include the essential role of starvation-induced autophagy in supplying nutrients such as amino acids, glucose, and free fatty acids for energy production and the synthesis of macromolecules. Furthermore, it has been established that autophagy selectively degrades intracellular components such as p62/SQSTM1- and ubiquitin-containing droplets, as well as damaged organelles for intracellular quality control in hepatic cells. Dysfunction of hepatic autophagy can lead to several liver diseases, including hepatic tumors. In this review, we describe the physiological role of hepatic autophagy and its pathophysiological significance in several chronic liver disorders.

Degradation of intracellular components through autophagy is a fundamental process to maintain cellular integrity and homeostasis. Recently, a glycogen-selective autophagy pathway has been described, termed ‘glycophagy’. Glycogen is a primary storage depot and regulator of glucose availability, and glycophagy is emerging as a critical physiological process involved in energy metabolism. Glycophagy-mediated degradation of glycogen appears to operate in parallel with the well-described canonical pathway of glycogenolysis involving glycogen phosphorylase. Evidence suggests that starch-binding domain protein 1 (Stbd1) is a key glycogen-binding protein involved in tagging glycogen for glycophagy, and that GABA Type A Receptor Protein Like 1 is primarily involved as the Atg8 family protein recruiting the Stbd1–glycogen complex into the forming glycophagosome. The nuances of glycophagy protein machinery, regulation, and lysosomal glucose release are yet to be fully elucidated. In this mini-review, we critically analyze the current evidence base for glycophagy as a selective-autophagy process of physiological importance and highlight areas where further investigation is warranted.

The endoplasmic reticulum (ER) is the largest cellular organelle that undergoes constant turnover upon diverse functional demands and cellular signals. Removal of nonfunctional or superfluous subdomains is balanced by the parallel expansion and formation of ER membranes, leading to the dynamic exchange of ER components. In recent years, selective autophagy of the ER, termed ER-phagy, has emerged as a predominant process involved in ER degradation and maintenance of ER homeostasis. Identification of multiple ER-phagy receptors, many with additional ER-shaping functions, paved the way for our molecular understanding of ER turnover in different cells and organs. In this review, we describe the molecular principles underling the physiological functions of ER-phagy in maintaining ER homeostasis via receptor-mediated macroautophagy and elaborate current focus points of the field.

Autophagy is a conserved catabolic process that delivers cytoplasmic materials to the lysosome for degradation. Recent studies indicate that autophagy is essential for maintaining vision by regulating intracellular homeostasis in various structures of the eye, including the lens, retina, cornea, and trabecular meshwork. Dysregulated autophagy causes ocular diseases such as cataract, glaucoma, retinitis pigmentosa, and age-related macular degeneration. Autophagy-independent degradation pathways such as LC3-associated phagocytosis in the retina and cytosolic PLAAT phospholipase-mediated organelle degradation in the lens are also physiologically important. Here, I summarize recent findings on the role of autophagy and related pathways in ocular physiology and disease.