Ubiquitination of ERMES components by the E3 ligase Rsp5 is involved in mitophagy

Belgareh‐Touzé, Naïma; Cavellini, Laetitia; Cohen, Mickaël M.

doi:10.1080/15548627.2016.1252889

Cited by 45 publications

(38 citation statements)

References 74 publications

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“…The latest studies have shown that mitochondria are targets of polyubiquitin [40, 41]. Studies have also shown that ubiquitinated PHB is present in mammalian sperm mitochondria, suggesting that this protein may mediate the ubiquitination of spermatozoa mitochondria [11].…”

Section: Discussionmentioning

confidence: 99%

Prohibitin-mediated mitochondrial ubiquitination during spermiogenesis in Chinese mitten crab Eriocheir sinensis

Hou

Wei

et al. 2017

Oncotarget

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The sperm of Eriocheir sinensis has a cup-shaped nucleus that contains several mitochondria embedded at the opening of the cup. The acrosome vesicle also contains derivants of mitochondria. The mitochondria distribution pattern involves a decrease in the number and changes in the structure and transportation of these organelles. The decreased number of sperm mitochondria is achieved through autophagy or the ubiquitination pathway. Prohibitin (PHB), the mitochondria inner membrane protein, is an evolutionarily highly conserved protein, is closely associated with spermatogenesis and sperm quality control and is also a potential substrate of ubiquitination. However, whether PHB protein mediates the ubiquitination pathway of sperm mitochondria in crustacean animals remains poorly understood. In the present study, we revealed that PHB, a substrate of ubiquitin, participates in the ubiquitination and degradation of mitochondria during spermiogenesis in E. sinensis. To confirm this finding, we used shRNA interference to reduce PHB expression and an overexpression technique to increase PHB expression in vitro. The interference experiment showed that the reduced PHB expression directly affected the polyubiquitination level and mitochondria status, whereas PHB overexpression markedly increased the polyubiquitination level. In vitro experiments also showed that PHB and its ubiquitination decide the fate of mitochondria.

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Section: Discussionmentioning

confidence: 99%

Prohibitin-mediated mitochondrial ubiquitination during spermiogenesis in Chinese mitten crab Eriocheir sinensis

Hou

Wei

et al. 2017

Oncotarget

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“…Additionally, mitochondria anchoring Gem1, a Ca 2+ -binding small GTPase, directly associates with the ERMES complex and regulates its size and number (14)(15)(16). ERMES components are also regulated by Rsp5 E3 ubiquitin ligase, and ubiquitination is required for efficient mitophagy (17).…”

mentioning

confidence: 99%

“…Furthermore, the ER membrane protein complex (EMC) comprising conserved Emc1-Emc6 proteins performs a comparable role in lipid transfer from the ER to mitochondria by mediating tethering between these organelles (26). In addition to lipid trafficking, other functions of the ERMES complex have been reported, including mitochondrial protein assembly (27) and import (28), maintenance of mitochondrial DNA (15,29,30), mitochondria inheritance (31), and mitophagy (17,(32)(33)(34).…”

mentioning

confidence: 99%

Crystal structures of Mmm1 and Mdm12–Mmm1 reveal mechanistic insight into phospholipid trafficking at ER-mitochondria contact sites

Jeong

Park

Jun

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

123

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The endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES) comprises mitochondrial distribution and morphology 12 (Mdm12), maintenance of mitochondrial morphology 1 (Mmm1), Mdm34, and Mdm10 and mediates physical membrane contact sites and nonvesicular lipid trafficking between the ER and mitochondria in yeast. Herein, we report two crystal structures of the synaptotagmin-like mitochondrial lipid-binding protein (SMP) domain of Mmm1 and the Mdm12-Mmm1 complex at 2.8 Å and 3.8 Å resolution, respectively. Mmm1 adopts a dimeric SMP structure augmented with two extra structural elements at the N and C termini that are involved in tight self-association and phospholipid coordination. Mmm1 binds two phospholipids inside the hydrophobic cavity, and the phosphate ion of the distal phospholipid is specifically recognized through extensive H-bonds. A positively charged concave surface on the SMP domain not only mediates ER membrane docking but also results in preferential binding to glycerophospholipids such as phosphatidylcholine (PC), phosphatidic acid (PA), phosphatidylglycerol (PG), and phosphatidylserine (PS), some of which are substrates for lipid-modifying enzymes in mitochondria. The Mdm12-Mmm1 structure reveals two Mdm12s binding to the SMP domains of the Mmm1 dimer in a pairwise head-to-tail manner. Direct association of Mmm1 and Mdm12 generates a 210-Å-long continuous hydrophobic tunnel that facilitates phospholipid transport. The Mdm12-Mmm1 complex binds all glycerophospholipids except for phosphatidylethanolamine (PE) in vitro.

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“…It is essential for viability that dysfunctional mitochondria are removed, which occurs via mitophagy 40 . Efficient mitophagy requires ubiquitination of the ERMES components Mdm34 and Mdm12 163 . Moreover, ERMES colocalizes with the site of mitophagosome generation and the ER was proposed to deliver the necessary lipids for membrane engulfment of the mitochondrion 164 165 .…”

Section: Ph Control Stress Tolerance and Longevitymentioning

confidence: 99%

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

Deprez¹,

Eskes²,

Wilms³

et al. 2018

Microb Cell

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The plasma membrane H+-ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

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Ubiquitination of ERMES components by the E3 ligase Rsp5 is involved in mitophagy

Cited by 45 publications

References 74 publications

Prohibitin-mediated mitochondrial ubiquitination during spermiogenesis in Chinese mitten crab Eriocheir sinensis

Prohibitin-mediated mitochondrial ubiquitination during spermiogenesis in Chinese mitten crab Eriocheir sinensis

Crystal structures of Mmm1 and Mdm12–Mmm1 reveal mechanistic insight into phospholipid trafficking at ER-mitochondria contact sites

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

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