The targeted anti-oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue

Gottwald, Esther Maria; Duss, Michael; Bugarski, Milica; Haenni, D.R.; Schuh, Claus D.; Landau, Ehud M.; Hall, Andrew M.

doi:10.14814/phy2.13667

Cited by 61 publications

(57 citation statements)

References 35 publications

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“…Besides normal tubular mitochondria, there are 2 special kinds of mitochondria generated by topological transformation: swollen and donut-shaped mitochondria. Various stresses can induce a shift from a tubular mitochondrial morphology to multiple round organelles with some or all swollen [22][23][24][25]. Mitochondrial swelling in relation to mitochondrial permeability transition pore (mPTP) opening has been observed, for example, during reoxygenation-reperfusion after hypoxia [26,27].…”

Section: Introductionmentioning

confidence: 99%

Topology-dependent, bifurcated mitochondrial quality control under starvation

Zhou

Long

et al. 2019

Autophagy

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Selective elimination of mitochondria by autophagy is a critical strategy for a variety of physiological processes, including development, cell-fate determination and stress response. Although several mechanisms have been identified as responsible for selective degradation of mitochondria, such as the PINK1-PRKN/PARKIN-and receptor-dependent pathways, aspects of the mechanisms and particularly the principles underlying the selection process of mitochondria remain obscure. Here, we addressed a new selection strategy in which the selective elimination of mitochondria is dependent on organellar topology. We found that populations of mitochondria undergo different topological transformations under serum starvation, either swelling or forming donut shapes. Swollen mitochondria are associated with mitochondrial membrane potential dissipation and PRKN recruitment, which promote their selective elimination, while the donut topology maintains mitochondrial membrane potential and helps mitochondria resist autophagy. Mechanistic studies show that donuts resist autophagy even after depolarization through preventing recruitment of autophagosome receptors CALCOCO2/NDP52 and OPTN even after PRKN recruitment. Our results demonstrate topology-dependent, bifurcated mitochondrial recycling under starvation, that is swollen mitochondria undergo removal by autophagy, while donut mitochondria undergo fission and fusion cycles for reintegration. This study reveals a novel morphological selection for control of mitochondrial quality and quantity under starvation.

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Section: Introductionmentioning

confidence: 99%

Topology-dependent, bifurcated mitochondrial quality control under starvation

Zhou

Long

et al. 2019

Autophagy

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“…As a third option, mitoQ may have increased ROS production and oxidative stress due to its long alkyl linker group ( Fig. S1; Maroz et al 2009;Reily et al 2013;Trnka et al 2015;Yasui et al 2017;Gottwald et al 2018). This may have promoted the consumption of tocopherol and xanthophylls to be used as radical scavengers (Britton et al 2004;Panda and Cherian 2014).…”

Section: Discussionmentioning

confidence: 99%

“…decyl-TPP + or dTPP + ). However, this chain length seems to favor membrane permeability, inhibiting the electron transport chain (ETC) and inducing higher superoxide radical generation (see Reily et al 2013;Trnka et al 2015;Gottwald et al 2018). Interestingly, zebra finches only treated with dTPP + developed paler bills than controls (Cantarero and Alonso-Alvarez 2017).…”

Section: The Antioxidant Treatmentmentioning

confidence: 99%

Testing the shared‐pathway hypothesis in the carotenoid‐based coloration of red crossbills

et al. 2020

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The mechanisms involved in the production of red carotenoid-based ornaments of vertebrates are still poorly understood. These colorations often depend on enzymatic transformations (ketolation) of dietary yellow carotenoids, which could occur in the inner mitochondrial membrane (IMM). Thus, carotenoid ketolation and cell respiration could share biochemical pathways, favoring the evolution of ketocarotenoid-based ornaments as reliable indices of individual quality under sexual selection. Captive male red crossbills (Loxia curvirostra Linnaeus) were exposed to redox-active compounds designed to penetrate and act in the IMM: an ubiquinone (mitoQ) or a superoxide dismutase mimetic (mitoTEMPO). MitoQ can act as an antioxidant but also distort the IMM structure, increasing mitochondrial free radical production. MitoQ decreased yellow carotenoids and tocopherol levels in blood, perhaps by being consumed as antioxidants. Contrarily, mitoTEMPO-treated birds rose circulating levels of the second most abundant ketocarotenoid in crossbills (i.e., canthaxanthin). It also increased feather total red ketocarotenoid concentration and redness, but only among those birds exhibiting a redder plumage at the start of the study, that is, supposedly high-quality individuals. The fact that mitoTEMPO effects depended on original plumage color suggests that the red-ketocarotenoid-based ornaments indicate individual quality as mitochondrial function efficiency. The findings would thus support the shared pathway hypothesis.

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“…This is likely to have improved the antioxidant action, avoiding disruption of the mitochondrial membrane and higher superoxide production (Reily et al . 2013; Trnka, Elkalaf & Anděl 2015; Gottwald et al . 2018).…”

Section: Discussionmentioning

confidence: 99%

“…The length of this molecule, however, increases membrane permeability, inhibiting the electron transport chain and rising superoxide radical generation (Reily et al . 2013; Trnka, Elkalaf & Anděl 2015; Gottwald et al . 2018).…”

Section: Introductionmentioning

confidence: 99%

A mitochondria-targeted antioxidant and a thyroid hormone affect carotenoid ketolase gene expression and bill redness in zebra finches

Cantarero

Andrade

Carneiro

et al. 2020

Preprint

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Conspicuous ornaments in animals can evolve to reveal individual quality when their production/maintenance costs make them reliable as signals or if their expression level is intrinsically linked to quality by some unfalsifiable mechanism (quality indices). The latter has been mostly associated with traits constrained by body size. However, red ketocarotenoid-based coloured ornaments may also have evolved as quality indices because their production could be closely linked to individual metabolism and, particularly, to the cell respiration at the inner mitochondrial membrane (IMM). This mechanism would supposedly not depend on resource (yellow carotenoids) availability, thus discarding allocation trade-offs. A gene coding for a ketolase enzyme (CYP2J19) responsible for converting dietary yellow carotenoids to red ketocarotenoids has recently been described in birds. It is not known, however, if this ketolase is involved in mitochondrial metabolism and if its expression level and activity is resource independent. Here, we manipulated the metabolism of captive male zebra finches by an antioxidant designed to penetrate the IMM (mitoTEMPO) and a thyroid hormone (triiodothyronine; T3) with known hypermetabolic effects. The expression levels of a ketocarotenoid-based ornament (bill redness) and CYP2J19 were measured. MitoTEMPO downregulated CYP2J19 expression, supporting the mitochondrial involvement in ketolase function. T3 also reduced CYP2J19 expression, but at an intermediate dosage, this effect being buffered by mitoTEMPO. Bill redness seemed to show a similar interacting effect. Nevertheless, this faded when CYP2J19 expression level was controlled for as a covariate. We argue that the well-known mitoTEMPO effect in reducing mitochondrial reactive oxygen species (ROS) production (particularly superoxide) could have interfered on redox signalling mechanisms controlling ketolase transcription. High T3 levels, contrarily, can lead to high ROS production but also trigger compensatory mechanisms, which may explain the U-shaped effect with dosage on CYP2J19 expression levels. Bill CYP2J19 expression values were also positively correlated to redness and circulating substrate carotenoid levels. Nonetheless, treatment effects did not change when controlling for blood carotenoid concentration, suggesting that resource-availability dependence was irrelevant. Finally, our findings reveal a role for thyroid hormones in the expression of carotenoid-based ornaments that has virtually been ignored until now.

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The targeted anti-oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue

Cited by 61 publications

References 35 publications

Topology-dependent, bifurcated mitochondrial quality control under starvation

Topology-dependent, bifurcated mitochondrial quality control under starvation

Testing the shared‐pathway hypothesis in the carotenoid‐based coloration of red crossbills

A mitochondria-targeted antioxidant and a thyroid hormone affect carotenoid ketolase gene expression and bill redness in zebra finches

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