The small <scp>GTP</scp>ase Arf1 modulates mitochondrial morphology and function

Ackema, Karin; Hench, Jürgen; Böckler, Stefan; Wang, Shyi Chyi; Sauder, Ursula; Mergentaler, Heidi; Westermann, Benedikt; Bard, Frédéric; Frank, Stephan; Spang, Anne

doi:10.15252/embj.201489039

Cited by 83 publications

(139 citation statements)

References 93 publications

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“…Furthermore, ARF1 was shown to genetically interact with GEM1; specifically, loss of Gem1 exacerbated the mitochondrial morphological phenotype associated with the arf1 mutant. These results suggested that Arf1 regulates ERMES functions, such as mitophagy [5]. However, it should be noted that Arf1 does not appear to be required for the physical tethering between the ER and mitochondria via ERMES.…”

mentioning

confidence: 89%

Arf1 and ER‐mitochondrial tethering – a new trick for an old dog

Davis

2018

The FEBS Journal

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Endoplasmic reticulum (ER)-mitochondria tethering by the ERMES complex is critical for numerous mitochondrial functions in fungi. It was recently discovered that the GTPase Arf1, which regulates within Golgi vesicular trafficking also affects ER-mitochondrial tethering potentially through ERMES. In Candida albicans, Arf1 not only functions in vesicular trafficking and affects ERMES but also impacts reactive oxygen species generation, which is a key immune defense molecule.

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confidence: 89%

Arf1 and ER‐mitochondrial tethering – a new trick for an old dog

Davis

2018

The FEBS Journal

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“…Previous reports have demonstrated that loss of ARF1 impaired mitochondrial morphology in mammalian and yeast cells . Herein, we observed mitochondrial morphology in the arf1 Δ/Δ cells with MitoTracker Red staining.…”

Section: Resultsmentioning

confidence: 61%

Arf1 regulates the ER–mitochondria encounter structure (ERMES) in a reactive oxygen species‐dependent manner

Zhang

Huo

et al. 2018

The FEBS Journal

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The Arf family of small GTP-binding and -hydrolyzing proteins are some of the most important intracellular regulators of membrane dynamics. In this study, we identified the Golgi-localized Arf family G protein Arf1 in Candida albicans and confirmed its conserved function in regulating the secretory pathway. Interestingly, deletion of ARF1 resulted in intracellular reactive oxygen species (ROS) accumulation, and induced formation of the endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES). Moreover, N-acetylcysteine-mediated ROS scavenging in the arf1Δ/Δ strain attenuated ERMES formation, indicating that intracellular ROS accumulation resulting from ARF1 deletion facilitated ERMES formation. In addition, Arf1 regulated many key physiological processes in C. albicans, including cell cycle progression, morphogenesis and virulence. This study uncovers a role for Arf family G proteins in regulating ERMES formation and sheds new light on the crucial contribution of ROS to membrane dynamics.

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“…GFB-1 and SGK-1 physically associate, being GBF-1 required for proper localization of SGK-1 near the basolateral membrane of intestinal cells [62]. Interestingly, ARF1 and GBF1 play an evolutionarily conserved role in ER-mitochondria contact site functionality and lack of GBF-1 causes a similar increase in mitochondrial size as sgk-1 deletion in C. elegans ([83] and Figure 1B and S1).…”

Section: Resultsmentioning

confidence: 99%

Prohibitin depletion extends lifespan of a TORC2/SGK-1 mutant through autophagy

Hernando‐Rodríguez

Pérez-Jiménez

Rodríguez-Palero

et al. 2019

Preprint

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13 14 -2 -Mitochondrial prohibitins (PHB) are highly conserved proteins with a peculiar 15 effect on lifespan. While PHB depletion shortens lifespan of wild type animals, it 16 enhances longevity of a plethora of metabolically compromised mutants, 17 including target of rapamycin complex 2 (TORC2) mutants sgk-1 and rict-1. Here, 18 we show that sgk-1 mutants have impaired mitochondrial homeostasis, 19 lipogenesis, yolk formation and autophagy flux due to alterations in membrane 20 lipid and sterol homeostasis. Remarkably, all these features are suppressed by 21 PHB depletion. Lifespan analysis shows that autophagy and the mitochondrial 22 unfolded protein response (UPR mt ), but not mitophagy, are required for the 23 enhanced longevity caused by PHB depletion in sgk-1 mutants. We hypothesize 24 that UPR mt induction upon PHB depletion extends lifespan of sgk-1 mutants 25 through autophagy. Our results strongly suggest that PHB depletion suppresses 26 the autophagy defects of sgk-1 mutants by altering membrane lipid composition 27 at ER-mitochondria contact sites, where TORC2 localizes. 28 29 93 mitochondria-associated endoplasmic reticulum (ER) membranes (MAM).94 95 -6 - Results 96Prohibitin depletion suppresses the altered mitochondrial structure and 97 function of sgk-1 mutants 98In C. elegans, loss of function of SGK-1 causes a delay in development (Jones et al., 992009) as well as reduced brood and body size (Soukas et al., 2009). These phenotypes 100 are consistent with phenotypes observed in mitochondrial mutants (Dillin et al., 2002). In 101 addition, worms lacking the TORC2 component RICT-1 or the downstream kinase SGK-102 1, have an induced mitochondrial unfolded protein response (UPR mt ) (Gatsi et al., 2014). 103We analyzed whether mitophagy, another mitochondrial quality control mechanism, 104 might be activated in sgk-1 deletion mutants using a mitophagy reporter based on PINK-105 1 protein (Kirienko et al., 2015). PINK-1 is a serine threonine protein kinase that, when 106 mitochondria are depolarized, accumulates in the outer mitochondrial membrane and 107 targets mitochondria for selective autophagy (Narendra and Youle, 2011; Palikaras et 108 al., 2015). We observed that depletion of sgk-1 increased PINK-1 protein levels ( Figure 109 1A). Similarly, PINK-1 protein levels increased upon depletion of phb-1 or atfs-1, the key 110 UPR mt regulator ( Figure 1A), confirming that sgk-1 mutants suffer from mitochondrial 111 stress. 112To better define the mitochondrial defect of sgk-1 deletion mutants we performed 113 transmission electron microscopy (TEM) analysis. Mitochondria in sgk-1 mutants were 114 swollen, and bigger compared to wild type worms in all tissues analyzed (hypodermis, 115 muscle and intestine) at both, day one and day five of adulthood ( Figure 1B and Figure 116 S1A, respectively). In contrast to previous observations (Zhou et al., 2019), no obvious 117 mitochondrial fragmentation or severe cristae defects in the intestine were observed in 118 the TEM sections analyzed. 119-7 -To ...

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The small GTPase Arf1 modulates mitochondrial morphology and function

Cited by 83 publications

References 93 publications

Arf1 and ER‐mitochondrial tethering – a new trick for an old dog

Arf1 and ER‐mitochondrial tethering – a new trick for an old dog

Arf1 regulates the ER–mitochondria encounter structure (ERMES) in a reactive oxygen species‐dependent manner

Prohibitin depletion extends lifespan of a TORC2/SGK-1 mutant through autophagy

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