Oroxylin a promotes PGC-1α/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease

20‐HETE synthesis inhibition attenuates traumatic brain injury–induced mitochondrial dysfunction and neuronal apoptosis via the SIRT1/PGC‐1α pathway: A translational study

“…40 Drp1 is one of the key mediators of mitochondrial fission, and Mfn1 and Mfn2 are two mitochondrial fusion regulators; all three proteins are regulated by PGC-1α. [41][42][43] In our study, HET0016 treatment reversed the increase in the expression of Drp1 and decrease in the expression of has proved that SIRT1 can activate PGC-1α, which contributes to enhanced mitochondrial biogenesis. 45,46 Angiotensin II-induced cardiomyocyte apoptosis is closely associated with mitochondrial fission, which in turn is closely associated with the SIRT1 signalling pathway.…”

Role of Mitofusins and Mitophagy in Life or Death Decisions

“…Necroptosis induction promoted ubiquitination and degradation of Mfn1, without affecting Mfn2 (Baker et al, 2014). Instead, upregulation of Mfn2 levels correlated with reduced pyroptosis in the liver, reverted by Oroxylin A, which allowed resisting to lipid deposition and ROS overproduction (Kai et al, 2020). In contrast, Mfn2 fusion activity was stimulated by the same BAX mutants that induced necrosis (Whelan et al, 2012;Karch et al, 2013) and hepatic knockdown of Mfn2 reduced ferroptosis, provoked by arsenite (Wei et al, 2020).…”

“…However, it is still under debate under which conditions Mfn2 acts as a spacer between both organelles, consistent with decreased distance observed in its absence ( Cosson et al, 2012 ; Filadi et al, 2015 ; Wang et al, 2015 ) or rather acts as an ER-mitochondria tether ( De Brito and Scorrano, 2008 ; Naon et al, 2016 ; Basso et al, 2018 ; McLelland et al, 2018 ). MFN2 has also been extensively linked to mitophagy ( Gegg et al, 2010 ; Poole et al, 2010 ; Ziviani et al, 2010 ), to apoptosis ( Karbowski et al, 2002 ; Brooks et al, 2007 ; Hoppins et al, 2011 ), as detailed below, and recently also to pyroptosis ( Kai et al, 2020 ) and ferroptosis ( Wei et al, 2020 ). Furthermore, MFN2 is believed to play multiple roles in metabolism, explaining its involvement in metabolic disorders such as obesity and diabetes mellitus ( Bach et al, 2005 ; Toledo et al, 2006 ; Sebastián et al, 2012 ; Schneeberger et al, 2014 ; Boutant et al, 2017 ; Ramiréz et al, 2017 ; Bell et al, 2019 ).…”

“…However, once released from the mitochondria into the cytoplasm, upon cristae opening, these pleiotropic proteins convert into apoptosis initiators, pushing the cell toward a deadly end (Snigirevskaya and Komissarchik, 2019). Besides apoptosis, mitochondria are also recognized by regulating other types of cell death such as necroptosis, ferroptosis, pyroptosis, and mitochondrial-mediated necrosis (Baines, 2010;Baker et al, 2014;Marshall and Baines, 2014;Battaglia et al, 2020;Kai et al, 2020;Wang et al, 2020;Wei et al, 2020). Finally, the IM encloses the mitochondrial matrix, where essential reactions take place, such as iron-sulfur cluster assembly (Cardenas et al, 2018;Lill, 2020) or the tricarboxylic acid (TCA) cycle, which feeds electrons to the respiratory chain and provides amino acid precursors (Mailloux et al, 2007;Martínez-Reyes and Chandel, 2020).…”

Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease

“…In addition to oxidative stress, multiple forms of cell death also play the considerable role in the complicated ALD pathogenesis. Recently, pyroptosis, a new type of inflammatory programmed cell death was discovered in ALD, which also provides new ideas for the treatment of ALD (Heo et al, 2019;Kai et al, 2020).…”