Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway

Tan, Ying; Ouyang, Haichun; Xiao, Xiaochan; Zhong, Jian‐Jiang; Dong, Maolong

doi:10.1007/s12192-019-00992-2

Cited by 43 publications

(22 citation statements)

References 65 publications

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“…Irisin, although discovered as a metabolic regulator, has been found to improve mitochondrial function and reduce ROS formation (Askari et al, 2018; Batirel, Bozaykut, Mutlu Altundag, Kartal Ozer, & Mantzoros, 2014; Bi et al, 2020; Bi, Zhang, Ren, Du, Li, Wang, Wei, et al, 2019; Bi, Zhang, Ren, Du, Li, Wang, Zhang, et al, 2019; Butt, Hackett, & Volkoff, 2017; Chen et al, 2017; de Oliveira Bristot, de Bem Alves, Cardoso, da Luz Scheffer, & Aguiar, 2019; Deng et al, 2018; Erden et al, 2016; J. Fan, Zhu, et al, 2019; Mazur‐Bialy, Kozlowska, Pochec, Bilski, & Brzozowski, 2018; Ren et al, 2019, 2020; Tan, Ouyang, Xiao, Zhong, & Dong, 2019; Z. Wang, Chen, et al, 2018). However, the effect of irisin on I/R‐induced AKI has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Involvement of GPX4 in irisin's protection against ischemia reperfusion‐induced acute kidney injury

Zhang

Ren

et al. 2020

Journal Cellular Physiology

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Ischemia reperfusion (I/R)-induced acute kidney injury (AKI) is a common and serious condition. Irisin, an exercise-induced hormone, improves mitochondrial function and reduces reactive oxygen species (ROS) production. Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis and its inactivation aggravates renal I/R injury by inducing ROS production. However, the effect of irisin on GPX4 and I/Rinduced AKI is still unknown. To study this, male adult mice were subjected to renal I/R by occluding bilateral renal hilum for 30 min, which was followed by 24 hr reperfusion. Our results showed serum irisin levels were decreased in renal I/R mice. Irisin (250 μg/kg) treatment alleviated renal injury, downregulated inflammatory response, improved mitochondrial function, and reduced ER stress and oxidative stress after renal I/R, which were associated with upregulation of GPX4. Treated with RSL3 (a GPX4 inhibitor) abolished irisin's protective effect. Thus, irisin attenuates I/R-induced AKI through upregulating GPX4.

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Section: Discussionmentioning

confidence: 99%

Involvement of GPX4 in irisin's protection against ischemia reperfusion‐induced acute kidney injury

Zhang

Ren

et al. 2020

Journal Cellular Physiology

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“…Irisin was also able to retain mitochondrial biogenesis, dynamics, and autophagic program in chondrocytes to repress inflammation-mediated oxidative stress and extracellular matrix underproduction [ 88 ]. Interestingly, irisin inhibits mitochondrial fission via the JNK-LATS2 pathway in cardiomyocytes [ 89 ] and hepatocytes [ 90 ] when excessive fission occurred during inflammation. Presumably, irisin may function as a beneficial effector of exercise to protect against excessive damage induced by inflammation.…”

Section: Myokines and Mitochondrial Dynamicsmentioning

confidence: 99%

Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

Pang¹,

Chan²,

Chan³

2021

Antioxidants

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Mitochondria are the cellular powerhouses that generate adenosine triphosphate (ATP) to substantiate various biochemical activities. Instead of being a static intracellular structure, they are dynamic organelles that perform constant structural and functional remodeling in response to different metabolic stresses. In situations that require a high ATP supply, new mitochondria are assembled (mitochondrial biogenesis) or formed by fusing the existing mitochondria (mitochondrial fusion) to maximize the oxidative capacity. On the other hand, nutrient overload may produce detrimental metabolites such as reactive oxidative species (ROS) that wreck the organelle, leading to the split of damaged mitochondria (mitofission) for clearance (mitophagy). These vital processes are tightly regulated by a sophisticated quality control system involving energy sensing, intracellular membrane interaction, autophagy, and proteasomal degradation to optimize the number of healthy mitochondria. The effective mitochondrial surveillance is particularly important to skeletal muscle fitness because of its large tissue mass as well as its high metabolic activities for supporting the intensive myofiber contractility. Indeed, the failure of the mitochondrial quality control system in skeletal muscle is associated with diseases such as insulin resistance, aging, and muscle wasting. While the mitochondrial dynamics in cells are believed to be intrinsically controlled by the energy content and nutrient availability, other upstream regulators such as hormonal signals from distal organs or factors generated by the muscle itself may also play a critical role. It is now clear that skeletal muscle actively participates in systemic energy homeostasis via producing hundreds of myokines. Acting either as autocrine/paracrine or circulating hormones to crosstalk with other organs, these secretory myokines regulate a large number of physiological activities including insulin sensitivity, fuel utilization, cell differentiation, and appetite behavior. In this article, we will review the mechanism of myokines in mitochondrial quality control and ROS balance, and discuss their translational potential.

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“…Additionally, a growing body of evidence supports that neuroinflammation and neurodegeneration can be initiated by robust inflammatory events in the periphery, including single dose lipopolysaccharide (LPS;Sheng et al, 2003;Kitazawa et al, 2005;Qin et al, 2007;Sy et al, 2011;Ifuku et al, 2012;Okuyama et al, 2013;Jin et al, 2014). Despite previous studies reporting altered mitochondrial dynamics in heart, lung, liver, kidney, and skeletal muscle tissue in sepsis animal models (Hansen et al, 2015;Liu et al, 2015;Yu et al, 2016;Park et al, 2018;Haileselassie et al, 2019;Tan et al, 2019), their role in the CNS during sepsis remains largely unknown. To examine this, we generated transgenic mice overexpressing Mfn2 specifically in CNS neurons under the control of Thy1.2 promotor, i.e., TMFN mice (Wang et al, 2015(Wang et al, , 2018 and investigated the role of neuronal Mfn2 in neuroinflammation by intraperitoneally injecting TMFN and age-matched nontransgenic (NTg) mice with LPS, one of the most widely used approaches for peripherally induced neuroinflammation (Catorce and Gevorkian, 2016), and explored the potential pathways by which neuronal mitochondria regulate neuroinflammation via Mfn2.…”

Section: Introductionmentioning

confidence: 99%

Neuronal Mitochondria Modulation of LPS-Induced Neuroinflammation

Harland¹,

Torres²,

Liu³

et al. 2020

J. Neurosci.

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Neuronal mitochondria dysfunction and neuroinflammation are two prominent pathological features increasingly realized as important pathogenic mechanisms for neurodegenerative diseases. However, little attempt has been taken to investigate the likely interactions between them. Mitofusin2 (Mfn2) is a mitochondrial outer membrane protein regulating mitochondrial fusion, a dynamic process essential for mitochondrial function. To explore the significance of neuronal mitochondria in the regulation of neuroinflammation, male and female transgenic mice with forced overexpression of Mfn2 specifically in neurons were intraperitoneally injected with lipopolysaccharide (LPS), a widely used approach to model neurodegeneration-associated neuroinflammation. Remarkably, LPS-induced lethality was almost completely abrogated in neuronal Mfn2 overexpression mice. Compared with nontransgenic wild-type mice, mice with neuronal Mfn2 overexpression also exhibited alleviated bodyweight loss, behavioral sickness, and myocardial dysfunction. LPS-induced release of IL-1␤ but not TNF-␣ was further found greatly inhibited in the CNS of mice with neuronal Mfn2 overexpression, whereas peripheral inflammatory responses in the blood, heart, lung, and spleen remained unchanged. At the cellular and molecular levels, neuronal Mfn2 suppressed the activation of microglia, prevented LPS-induced mitochondrial fragmentation in neurons, and importantly, upregulated the expression of CX3CL1, a unique chemokine constitutively produced by neurons to suppress microglial activation. Together, these results reveal an unrecognized possible role of neuronal mitochondria in the regulation of microglial activation, and propose neuronal Mfn2 as a likely mechanistic linker between neuronal mitochondria dysfunction and neuroinflammation in neurodegeneration.

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Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway

Cited by 43 publications

References 65 publications

Involvement of GPX4 in irisin's protection against ischemia reperfusion‐induced acute kidney injury

Involvement of GPX4 in irisin's protection against ischemia reperfusion‐induced acute kidney injury

Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

Neuronal Mitochondria Modulation of LPS-Induced Neuroinflammation

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