Pex19 is involved in importing dually targeted tail‐anchored proteins to both mitochondria and peroxisomes

Cichocki, B.; Krumpe, Katrin; Vitali, Daniela G.; Rapaport, Doron

doi:10.1111/tra.12604

Cited by 49 publications

(49 citation statements)

References 73 publications

(104 reference statements)

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“…Recent work in yeast has identified the cytosolic chaperones ssc1 and ssc2 as potential factors required for targeting of C-terminally anchored proteins to the OMM [63]. Recent work in yeast has identified the cytosolic chaperones ssc1 and ssc2 as potential factors required for targeting of C-terminally anchored proteins to the OMM [63].…”

Section: Discussionmentioning

confidence: 99%

“…Though Pex19 is known to be the chaperone required for the peroxisomal targeting of C-terminally anchored proteins (such as Miro), the targeting of C-terminally anchored proteins to the mitochondria is less well understood. Recent work in yeast has identified the cytosolic chaperones ssc1 and ssc2 as potential factors required for targeting of C-terminally anchored proteins to the OMM [63]. Interestingly, Cichocki et al [63] also show that the loss of Pex19 impinges upon mitochondrial targeting.…”

Section: Discussionmentioning

confidence: 99%

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Peroxisomal fission is modulated by the mitochondrial Rho‐GTPases, Miro1 and Miro2

et al. 2020

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Peroxisomes are essential for a number of cellular functions, including reactive oxygen species metabolism, fatty acid b-oxidation and lipid synthesis. To ensure optimal functionality, peroxisomal size, shape and number must be dynamically maintained; however, many aspects of how this is regulated remain poorly characterised. Here, we show that the localisation of Miro1 and Miro2-outer mitochondrial membrane proteins essential for mitochondrial trafficking-to peroxisomes is not required for basal peroxisomal distribution and long-range trafficking, but rather for the maintenance of peroxisomal size and morphology through peroxisomal fission. Mechanistically, this is achieved by Miro negatively regulating Drp1-dependent fission, a function that is shared with the mitochondria. We further find that the peroxisomal localisation of Miro is regulated by its first GTPase domain and is mediated by an interaction through its transmembrane domain with the peroxisomal-membrane protein chaperone, Pex19. Our work highlights a shared regulatory role of Miro in maintaining the morphology of both peroxisomes and mitochondria, supporting a crosstalk between peroxisomal and mitochondrial biology.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Peroxisomal fission is modulated by the mitochondrial Rho‐GTPases, Miro1 and Miro2

et al. 2020

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“…Several TA proteins exhibit dual targeting to peroxisomes and mitochondria. Pex3 and Pex19 are involved in sorting of TA proteins to peroxisomes (e.g., Pex15 , Fis1 , Gem1 ). Recently, Cichocki et al .…”

Section: Alternative Functions Of Pex3 and Pex19mentioning

confidence: 99%

“…Pex19 facilitates targeting to mitochondrial outer membrane and peroxisome [93] Mammalian cell line (COS-7) hFis1…”

Section: S Cerevisiae Fis1 Gem1mentioning

confidence: 99%

“…Pex3 and Pex19 are involved in sorting of TA proteins to peroxisomes (e.g., Pex15 [90][91][92], Fis1 [93], Gem1 [93]). Recently, Cichocki et al [93] demonstrated that, in S. cerevisiae, Pex19 associates with both peroxisomes and mitochondria and plays a role in sorting dually targeted Fis1 and Gem1 both to peroxisomes and mitochondria. Mammalian Fis1 sorting to peroxisomes has also been demonstrated to depend on PEX19, but mitochondrial Fis1 targeting is independent of PEX19 [94].…”

Section: Dual Targeting Of Ta Proteins To Peroxisomes and Mitochondriamentioning

confidence: 99%

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The peroxisome biogenesis factors Pex3 and Pex19: multitasking proteins with disputed functions

Jansen

Klei

2019

FEBS Letters

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The peroxisomal membrane protein (PMP) Pex3 and its cytosolic interaction partner Pex19 have been implicated in peroxisomal membrane biogenesis. Although these peroxins have been extensively studied, no consensus has been reached yet on how they operate. Here, we discuss two major models of their function, namely, in direct insertion of proteins into the peroxisomal membrane or in formation of PMP‐containing vesicles from the endoplasmic reticulum (ER). Pex3 can also recruit other proteins to the peroxisomal membrane (e.g., Inp1, Atg30, Atg36), thereby fulfilling roles in other processes such as autophagy and organelle retention. Recent studies indicate that Pex3 and Pex19 can also facilitate sorting of certain membrane proteins to other cellular organelles, including the ER, lipid droplets, and mitochondria.

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Regulation of peroxisomal trafficking and distribution

Covill‐Cooke

Toncheva

Kittler

2020

Cell. Mol. Life Sci.

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Peroxisomes are organelles that perform a wide range of essential metabolic processes. To ensure that peroxisomes are optimally positioned in the cell, they must be transported by both long- and short-range trafficking events in response to cellular needs. Here, we review our current understanding of the mechanisms by which the cytoskeleton and organelle contact sites alter peroxisomal distribution. Though the focus of the review is peroxisomal transport in mammalian cells, findings from flies and fungi are used for comparison and to inform the gaps in our understanding. Attention is given to the apparent overlap in regulatory mechanisms for mitochondrial and peroxisomal trafficking, along with the recently discovered role of the mitochondrial Rho-GTPases, Miro, in peroxisomal dynamics. Moreover, we outline and discuss the known pathological and pharmacological conditions that perturb peroxisomal positioning. We conclude by highlighting several gaps in our current knowledge and suggest future directions that require attention.

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Pex19 is involved in importing dually targeted tail‐anchored proteins to both mitochondria and peroxisomes

Cited by 49 publications

References 73 publications

Peroxisomal fission is modulated by the mitochondrial Rho‐GTPases, Miro1 and Miro2

Peroxisomal fission is modulated by the mitochondrial Rho‐GTPases, Miro1 and Miro2

The peroxisome biogenesis factors Pex3 and Pex19: multitasking proteins with disputed functions

Regulation of peroxisomal trafficking and distribution

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