摘要：
Mitochondrial unfolded protein response (UPRmt) is a mitochondria stress response, which the transcriptional activation programs of mitochondrial chaperone proteins and proteases are initiated to maintain proteostasis in mitochondria. Additionally, the activation of UPRmt delays aging and extends lifespan by maintaining mitochondrial proteostasis. Growing evidences suggests that UPRmt plays an important role in diverse human diseases, especially ageing-related diseases. Therefore, this review focuses on the role of UPRmt in ageing and ageing-related neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and Parkinson's disease. The activation of UPRmt and the high expression of UPRmt components contribute to longevity extension. The activation of UPRmt may ameliorate Alzheimer's disease, Parkinson's disease and Huntington's disease. Besides, UPRmt is also involved in the occurrence and development of cancers and heart diseases. UPRmt contributes to the growth, invasive and metastasis of cancers. UPRmt has paradoxical roles in heart diseases. UPRmt not only protects against heart damage, but may sometimes aggravates the development of heart diseases. Considering the pleiotropic actions of UPRmt system, targeting UPRmt pathway may be a potent therapeutic avenue for neurodegenerative diseases, cancers and heart diseases.
摘要：
<jats:title>Abstract</jats:title><jats:p>N<jats:sup>6</jats:sup>‐methyladenosine (m<jats:sup>6</jats:sup>A) is one of the most common internal modifications in messenger RNA, which is necessary for cell physiological activities. A recent study shows that during mammalian hematopoietic development, loss of m<jats:sup>6</jats:sup>A modification leads to the aberrant production of double‐stranded RNA, which results in the abnormal activation of innate immune response, and ultimately leads to hematopoietic failure. Accordingly, m<jats:sup>6</jats:sup>A modification provide us an attractive direction for us to understand mammalian hematopoietic development and innate immune response.</jats:p>
摘要：
Iron is one of the most important elements for life, but excess iron is toxic. Intracellularly, mitochondria are the center of iron utilization requiring sufficient amounts to maintain normal physiologic function. Accordingly, disruption of iron homeostasis could seriously impact mitochondrial function leading to impaired energy state and potential disease development. In this review, we discuss mechanisms of iron metabolism including transport, processing, heme synthesis, iron-sulfur cluster biogenesis and storage. We highlight the vital role of mitochondrial iron in pathologic states including neurodegenerative disorders and sideroblastic anemia.
作者机构：
[Lingzhi Wang; Jinyong Jiang; Linxi Chen] Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China;[Qun Zhou] Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 418000, China
通讯机构：
[Linxi Chen; Jinyong Jiang] I;Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang 421001, China
关键词：
aging;iron;mitochondria
摘要：
A recent study by Hughes et al. [1] showed that cysteine-mediated iron deficiency is the main cause of aging-related mitochondrial dysfunction. They also uncovered that aging-induced vacuolar/lysosomal de-acidification participates in the cysteine-mediated iron deficiency, implying that the de-acidifying lysosome triggers vacuolar/lysosomal dysfunction and iron deficiency, further leading to mitochondrial dysfunction. Previous studies showed that iron and lysosomal-mitochondrial crosstalk are the two important mechanisms that lysosome regulates aging, and it is well known that iron plays a pivotal role in various cell metabolic activities [2,3]. Accumulating evidence shows that there is a close relationship between lysosome and mitochondria, yet little is known about the exact role of them. The discovery that iron deficiency mediates lysosomal-mitochondrial crosstalk has presented a new therapeutic avenue for managing aging and aging-related diseases.
摘要：
Cardiovascular disease (CVD) leads to high morbidity and mortality rates worldwide. Accumulating evidence has revealed that mitochondria dysfunction is implicated in CVD, such as atherosclerosis (AS), hypertension, myocardial ischemia-reperfusion (MI/R) injury, myocardial infarction (MI), cardiac hypertrophy, heart failure (HF), dilated cardiomyopathy (DCM) and so on. Mitophagy is a mitochondrial quality control mechanism that eliminates damaged or superfluous mitochondria to maintain cardiac function in response to various stress and cardiac disease conditions. This article reviews the latest findings regarding the mechanistic, functional, and potential role of mitophagy in the pathogenesis of CVD. Moreover, various drugs can target mitophagy activity during CVD progression. Thus, the modulation of the mitophagy pathway provides a potential therapeutic strategy for CVD management.
作者机构：
[Li Zhu; Qionglin Zhou; Linxi Chen] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China;[Lu He] Department of Pharmacy, The First Affiliated Hospital, University of South China, Hengyang 421001, China
通讯机构：
[Lu He] D;[Linxi Chen] I;Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang 421001, China<&wdkj&>Department of Pharmacy, The First Affiliated Hospital, University of South China , Hengyang 421001, China
关键词：
signal transduction;glycolysis;oxidative phosphorylation
摘要：
Iron regulatory protein 2 (IRP2), first separated from mouse in 1993,is a cytoplasmic iron-regulated RNA-binding protein. IRP2 is a subtype of iron regulatory proteins (IRPs). IRP2 binds to ironresponsive element (IRE) RNA sequence to maintain iron homeostasis [1]. IRP2 can easily be hydrolyzed by protease because of its unique sequence of 73 amino acids. In general, IRP2 is widely expressed in many tissues, including fat, lung, brain, stomach, liver, heart, thyroid, adrenal, lymph node, kidney, intestine and so on [2].
摘要：
The present review is a summary of the recent literature concerning Bnip3 expression, function, and regulation, along with its implications in mitochondrial dysfunction, disorders of mitophagy homeostasis, and development of diseases of secondary mitochondrial dysfunction. As a member of the Bcl-2 family of cell death-regulating factors, Bnip3 mediates mPTP opening, mitochondrial potential, oxidative stress, calcium overload, mitochondrial respiratory collapse, and ATP shortage of mitochondria from multiple cells. Recent studies have discovered that Bnip3 regulates mitochondrial dysfunction, mitochondrial fragmentation, mitophagy, cell apoptosis, and the development of lipid disorder diseases via numerous cellular signaling pathways. In addition, Bnip3 promotes the development of cardiac hypertrophy by mediating inflammatory response or the related signaling pathways of cardiomyocytes and is also responsible for raising abnormal mitophagy and apoptosis progression through multiple molecular signaling pathways, inducing the pathogenesis and progress of hepatocellular carcinoma (HCC). Different molecules regulate Bnip3 expression at both the transcriptional and post-transcriptional level, leading to mitochondrial dysfunction and unbalance of mitophagy in hepatocytes, which promotes the development of non-alcoholic fatty liver disease (NAFLD). Thus, Bnip3 plays an important role in mitochondrial dysfunction and mitophagy homeostasis and has emerged as a promising therapeutic target for diseases of secondary mitochondrial dysfunction.
作者机构：
[Zhao Hong; Chen Lin Xi] Univ South China, Hengyang Med Coll, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Zhao Hong; Qiu Ting Ting] Univ South China, Coll Nursing, Hengyang 421001, Hunan, Peoples R China.;[Liu Mei Qing] Second Peoples Hosp Yunnan Prov, Dept Pharm, Kunming 650000, Yunnan, Peoples R China.
通讯机构：
[Chen Lin Xi] U;[Liu Mei Qing] S;Univ South China, Hengyang Med Coll, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;Second Peoples Hosp Yunnan Prov, Dept Pharm, Kunming 650000, Yunnan, Peoples R China.
关键词：
STORE;producing;FEEDING
摘要：
Mammalian adipose tissues can be broadly divided into white adipose tissue(WAT), beige adipose tissue, and brown adipose tissue(BAT)[1]. The function of WAT is to store superfluous energy and is characterized by unilamellar lipid droplets. WAT, as a prominent endocrine organ, regulates feeding and satiety by producing hormones. Compared with WAT, beige adipose tissue has some smaller multilocular lipid droplets and is located in WAT depots. However, BAT contains an abundance of mitochondria, uncoupling protein-1(UCP1), and multilocular lipid droplets[2]. BAT is an important non-shivering thermogenesis organ, with the capacity to oxidize metabolic substrates, including fatty acids and glucose, to produce heat. The main mechanism of heat production depends on UCP1. It transports protons into mitochondria, leading to the collapse of the proton gradient for oxidative phosphorylation; subsequently, cells generate heat instead of ATP. The thermogenic activity of brown adipocytes enables them to safeguard other tissues and themselves from lipid overaccumulation. Many studies have confirmed that promoting brown adipose thermogenic activity or the browning of white fat contributes to curbing obesity, diabetes,and other metabolic diseases[3-7]. Brown adipocytes are derived from Myf5+ progenitors with a high expression of PRDM16, BMP7, and PPARγ. These transcription regulators drive progenitors to develop into mature brown adipocytes[8]. Meanwhile, a development process is required for brown adipogenesis to suppress adipogenic inhibitors,including Wnt, necdin, and preadipocyte factor-1(Pref-1). Numerous studies have confirmed that many signaling pathways promote brown adipocyte differentiation, including rhACE2, SIRT5, RGS2,STAT3, RepSox, and SENP2(Figure 1). Tu et al.[9] reported that RepSox promoted brown preadipocyte differentiation by inhibiting TGF-β signaling. Shuai et al.[10] demonstrated that SIRT5 enhanced the expression of brown adipogenic promoters, including PPARγ and PRDM16. Klepac et al.[11] identified a crucial role for RGS2, which antagonized the inhibitory effect of Gq/Rho/ROCK signaling, in the acceleration brown adipogenesis. Cantwell et al.[12] revealed the significance of STAT3 in the early induction of primary Myf5+ brown adipogenesis through its suppression of Wnt/β-catenin signaling. Kawabe et al.[13] proved that rhACE2 increased the levels of PRDMl6 and PGC1α to boost differentiation of BAT. Recently, Liang et al.[14] demonstrated that brown adipocyte differentiation was facilitated via the SENP2-mediated deSUMOylation for necdin.
摘要：
A recent study suggests that voltage-dependent anion channel (VDAC) oligomer pores promote mitochondrial outer membrane permeabilization (MOMP) and allow mtDNA to be released into the cytosol in live cells. It challenges the notion that only occurs in apoptotic cells via BAX/BAK macropores. Cytosolic mtDNA activates cyclic GMP-AMP synthase (cGAS) / Stimulator of IFN Gene (STING) pathway and triggers type I interferon (IFN) response thereafter, which ultimately causes systemic lupus erythematosus (SLE). Mechanistically, mtDNA can interact with three positively charged residues (Lys12, Arg15, and Lys20) at the N-terminus of VDAC1, thereby strengthening VDAC1 oligomerization and facilitating mtDNA release. Additionally, there are other pathways that can mediate mtDNA release, such as BAX/BAK macropores and virus-derived pores. The mtDNA released into the cytosol also triggers type I IFN response via the generally accepted cGAS-STING-TANK-binding kinase 1(TBK1)-IFN regulatory factor 3 (IRF-3) axis. Collectively, VDAC oligomer pores provide us an attractive direction for us to understand mtDNA release-related diseases. This article is protected by copyright. All rights reserved.
通讯机构：
[Chen, LX; Li, LF] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词：
Berberine;Cardiovascular diseases;Endoplasmic reticulum stress;Ischemia reperfusion injury;Schisandrin B;Unfolded protein response
摘要：
Endoplasmic reticulum (ER) is an intracellular membranous organelle involved in the synthesis, folding, maturation and post-translation modification of secretory and transmembrane proteins. Therefore, ER is closely related to the maintenance of intracellular homeostasis and the good balance between health and diseases. Endoplasmic reticulum stress (ERS) occurs when unfolded/misfolded proteins accumulate after disturbance of ER environment. In response to ERS, cells trigger an adaptive response called the Unfolded protein response (UPR), which helps cells cope with the stress. In recent years, a large number of studies show that ERS can aggravate cardiovascular diseases. ERS-related proteins expression in cardiovascular diseases is on the rise. Therefore, down-regulation of ERS is critical for alleviating symptoms of cardiovascular diseases, which may be used in the near future to treat cardiovascular diseases. This article reviews the relationship between ERS and cardiovascular diseases and drugs that inhibit ERS. Furthermore, we detail the role of ERS inhibitors in the treatment of cardiovascular disease. Drugs that inhibit ERS are considered as promising strategies for the treatment of cardiovascular diseases.
作者机构：
[Yiyuan Yang; Lanfang Li; Kai Zhang; Linxi Chen] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
通讯机构：
[Linxi Chen; Lanfang Li] I;Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
摘要：
Cardiomyocytes, also known as myocardial fibers, are the muscle cells which form the heart tissue. Previous studies have indicated that fetal mammalian cardiomyocytes maintain the regeneration capacity, which promotes the fetal heart growth. Regardless of environment insults including nutrient deprivation, changes of blood flow, along with mechanical and volume loading [1], embryonic mammalian cardiac muscle cells are also related to robust proliferation response. Similarly, the hearts of 1-day-old neonatal mice could also be fully regenerated after surgical resection of the left ventricular apex or myocardial infarction (MI) [2]. Intriguingly, studies have also shown that certain fish, such as adult zebrafish, or urodele amphibians retain an observable capacity for regeneration [3]. In response to cardiac damage, zebrafish exhibits complete regeneration primarily due to the proliferation of cardiomyocytes. Nevertheless, the mouse heart loses this potential in the first week after birth. Tragically, it has been demonstrated that the adult mammalian cardiomyocyte unable to proliferate (Fig. 1A). Adult heart is considered as a terminally differentiated organ [4] that has limited capacity for cardiomyogenesis. Therefore, patients suffering from cardiovascular failure are unable to repair the heart and survive after MI or other heart diseases. Therefore, finding a feasible approach to stimulate adult mammalian cardiomyocyte proliferation is beneficial for the treatment of MI and other heart diseases.
