Mitochondrial aquaporin-8 is involved in SREBP-controlled hepatocyte cholesterol biosynthesis

Danielli, Mauro; Marrone, Julieta; Capiglioni, Alejo M.; Marinelli, Raúl A.

doi:10.1016/j.freeradbiomed.2018.12.016

Cited by 19 publications

(13 citation statements)

References 45 publications

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“…The siRNA1 and siRNA2 were targeted to two different regions of the rat AQP8 molecule. Corresponding control siRNA (SCR) was designed by randomly scrambling the nucleotides of siRNA1 [1], [2]. After 18 h of culture, hepatic cells were transfected with siRNAs by using Lipofectamine 2000 transfection reagent following the manufacturer instructions.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…After 24 and 48 h of transfection, cells were sonicated in 0.3 M sucrose containing 0.1 mM phenylmethanesulfonyl fluoride and 0.1 mM leupeptin and a 6000× g postnuclear mitochondrial fractions was prepared [2], [3]. Hepatocyte viability assessed by lactate dehydrogenase leakage was unaffected after at 24 or 48 h of transfection with siRNAs [1].…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…Mitochondria were isolated from primary rat hepatocytes transfected for 24 or 48 h with siRNA specific for rat AQP8 or control scramble (SCR) (see Experimental design, materials and methods for details). The mtAQP8 protein expression was unaltered at 24 h but significantly decreased around 60% at 48 h [1]. Left: Time course of H 2 O 2 release from mitochondria isolated from AQP8-knockdown hepatocytes (i.e., 48 h post-transfection).…”

Section: Datamentioning

confidence: 99%

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Data of H2O2 release from AQP8-knockdown rat hepatocyte mitochondria

et al. 2019

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This article reports experimental data related to the research article entitled “Mitochondrial aquaporin-8 is involved in SREBP-controlled hepatocyte cholesterol biosynthesis” [Danielli et al., 2019]. We present data about hydrogen peroxide (H 2 O 2 ) release from mitochondria isolated from rat hepatocytes with or without silencing of aquaporin-8 (AQP8) protein expression. The rate of mitochondrial H 2 O 2 release (pmoles/min/mg mitochondrial protein) was found to be decreased by about 50% in AQP8-knockdown mitochondria.

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Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Section: Datamentioning

confidence: 99%

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Data of H2O2 release from AQP8-knockdown rat hepatocyte mitochondria

et al. 2019

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“…Interestingly, mammalian AQP8 appears to have the largest H 2 O 2 permeability ( Bienert et al, 2007 ). Genetic manipulation of mitochondrial AQP8 supports its role in H 2 O 2 release to the cytosol ( Danielli et al, 2019a , b ), which could contribute to Cd-induced cell death.…”

Section: And Kidney Mitochondrial Damagementioning

confidence: 94%

Iron and Cadmium Entry Into Renal Mitochondria: Physiological and Toxicological Implications

Thévenod

Lee

Garrick

2020

Front. Cell Dev. Biol.

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Regulation of body fluid homeostasis is a major renal function, occurring largely through epithelial solute transport in various nephron segments driven by Na + /K + -ATPase activity. Energy demands are greatest in the proximal tubule and thick ascending limb where mitochondrial ATP production occurs through oxidative phosphorylation. Mitochondria contain 20–80% of the cell’s iron, copper, and manganese that are imported for their redox properties, primarily for electron transport. Redox reactions, however, also lead to reactive, toxic compounds, hence careful control of redox-active metal import into mitochondria is necessary. Current dogma claims the outer mitochondrial membrane (OMM) is freely permeable to metal ions, while the inner mitochondrial membrane (IMM) is selectively permeable. Yet we recently showed iron and manganese import at the OMM involves divalent metal transporter 1 (DMT1), an H + -coupled metal ion transporter. Thus, iron import is not only regulated by IMM mitoferrins, but also depends on the OMM to intermembrane space H + gradient. We discuss how these mitochondrial transport processes contribute to renal injury in systemic (e.g., hemochromatosis) and local (e.g., hemoglobinuria) iron overload. Furthermore, the environmental toxicant cadmium selectively damages kidney mitochondria by “ionic mimicry” utilizing iron and calcium transporters, such as OMM DMT1 or IMM calcium uniporter, and by disrupting the electron transport chain. Consequently, unraveling mitochondrial metal ion transport may help develop new strategies to prevent kidney injury induced by metals.

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“…However, the mitochondrial matrix also contains a robust system that converts superoxide to H2O2 (SOD2), and several peroxidases that regulate the level of H2O2 in the matrix (59). While the mitochondrial inner membrane is impermeable to both superoxide and H2O2 (60), a water channel, aquaporin 8 (AQP8), allows the diffusion of H2O2 to the outer compartment (61), and eventually, through VDAC to the cytoplasm. That flow of H2O2 from the mitochondria to the cytoplasm largely controls the redox balance in the cytoplasm.…”

Section: Aging and Enhanced Mptp Activitymentioning

confidence: 99%

The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity

Rottenberg¹,

Hoek²

2020

Preprint

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The activity of the mitochondrial Permeability Transition Pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging Reactive Oxygen Species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either, inhibit, or accelerate aging, retards, or enhance the progression of aging-driven degenerative diseases, and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Diseases. The Increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.

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Mitochondrial aquaporin-8 is involved in SREBP-controlled hepatocyte cholesterol biosynthesis

Cited by 19 publications

References 45 publications

Data of H2O2 release from AQP8-knockdown rat hepatocyte mitochondria

Data of H2O2 release from AQP8-knockdown rat hepatocyte mitochondria

Iron and Cadmium Entry Into Renal Mitochondria: Physiological and Toxicological Implications

The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity

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