Three Distinct Types of Microautophagy Based on Membrane Dynamics and Molecular Machineries

Oku, Masahide; Sakai, Yasuyoshi

doi:10.1002/bies.201800008

Cited by 190 publications

(163 citation statements)

References 50 publications

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“…In order to frame our current knowledge of ER‐phagy, key general autophagy principles are outlined below. More can be found in dedicated review articles . This review focuses on mammals.…”

Section: Overview Of Autophagymentioning

confidence: 99%

“…In microautophagy, endosomes or lysosomes (the vacuole in yeast), can invaginate to subsume cargo. Alternatively, lysosome or vacuole membranes can protrude to enwrap cargo . Microautophagy pathways employ diverse molecular mechanisms.…”

Section: Overview Of Autophagymentioning

confidence: 99%

“…Two main forms of autophagy regulate ER status. In microautophagy, sequestration of cytoplasmic material occurs via engulfment into endosomes or lysosomes . Conversely, macroautophagy sequesters cytoplasm in nascent phagocytic vesicles, called autophagosomes, which fuse with lysosomes .…”

Section: Introductionmentioning

confidence: 99%

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ER‐phagy: shaping up and destressing the endoplasmic reticulum

2019

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The endoplasmic reticulum (ER) network has central roles in metabolism and cellular organization. The ER undergoes dynamic alterations in morphology, molecular composition and functional specification. Remodelling of the network under fluctuating conditions enables the continual performance of ER functions and minimizes stress. Recent data have revealed that selective autophagy‐mediated degradation of ER fragments, or ER‐phagy, fundamentally contributes to this remodelling. This review provides a perspective on established views of selective autophagy, comparing these with emerging mechanisms of ER‐phagy and related processes. The text discusses the impact of ER‐phagy on the function of the ER‐ and the cell, both in normal physiology and when dysregulated within disease settings. Finally, unanswered questions regarding the mechanisms and significance of ER‐phagy are highlighted.

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Section: Overview Of Autophagymentioning

confidence: 99%

Section: Overview Of Autophagymentioning

confidence: 99%

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ER‐phagy: shaping up and destressing the endoplasmic reticulum

2019

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“…First, the term 'microautophagy' likely conflates distinct types of autophagy (Schuck et al, 2014;Oku and Sakai, 2018). Second, microautophagy may in some settings indirectly depend on the core autophagy machinery.…”

Section: Introductionmentioning

confidence: 99%

ESCRT machinery mediates selective microautophagy of endoplasmic reticulum

Schäfer

Schessner

Bircham

et al. 2019

Preprint

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ER‐phagy, the selective autophagy of endoplasmic reticulum (ER), safeguards organelle homeostasis by eliminating misfolded proteins and regulating ER size. ER‐phagy can occur by macroautophagic and microautophagic mechanisms. While dedicated machinery for macro‐ER‐phagy has been discovered, the molecules and mechanisms mediating micro‐ER‐phagy remain unknown. Here, we first show that micro‐ER‐phagy in yeast involves the conversion of stacked cisternal ER into multilamellar ER whorls during microautophagic uptake into lysosomes. Second, we identify the conserved Nem1‐Spo7 phosphatase complex and the ESCRT machinery as key components for micro‐ER‐phagy. Third, we demonstrate that macro‐ and micro‐ER‐phagy are parallel pathways with distinct molecular requirements. Finally, we provide evidence that the ESCRT machinery directly functions in scission of the lysosomal membrane to complete the microautophagic uptake of ER. These findings establish a framework for a mechanistic understanding of micro‐ER‐phagy and, thus, a comprehensive appreciation of the role of autophagy in ER homeostasis.

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“…Microautophagy is a general term for vacuolar/lysosomal membrane protrusions or invaginations for the direct uptake of cytosol, large protein assemblies, (parts of) organelles such as the ER, or resident membrane proteins (Müller et al, 2000;Schuck et al, 2014;Roberts et al, 2003;Kiššová et al, 2007;van Zutphen et al, 2014;Oku and Sakai, 2018;Zhu et al, 2017). Invaginations from the vacuolar/lysosomal membrane were recently shown to require some ESCRT components and might thus be mechanistically related to the endosomal MVB pathway (Oku et al, 2017;Oku and Sakai, 2018). The extent to which ESCRT components are generally involved in membrane invaginations from the vacuole/lysosome is still unclear at present.…”

Section: Introductionmentioning

confidence: 99%

A post-ER degradation pathway that relies on protease-dependent internalization from the vacuolar membrane

Lemus

Matić

Goder

2019

Preprint

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2 Abbreviations: GPI anchor: glycosylphophatidylinositol anchor; ESCRT: endosomal sorting complexes required for transport; MVBs: multi vesicular bodies; ILVs: intraluminal vesicles; ERAD: endoplasmic reticulum-associated protein degradation; TMD: transmembrane domain; PVC: prevacuolar compartment; SNARE: soluble NSF attachment protein receptor; Cvt vesicle: cytoplasm to vacuole targeting vesicle Keywords: Protein degradation, secretory pathway, vacuole, vacuolar protease, membrane invagination Highlights: • ER-exited misfolded GPI-anchored proteins are routed to the vacuole via endosomes but do not internalize into intraluminal vesicles • Internalization occurs directly from the vacuolar membrane into intravacuolar mobile structures • Internalization from the vacuolar membrane depends on the proteolytic activity of the vacuolar protease Pep4 3 Summary Newly synthesized proteins of the secretory pathway are quality-controlled inside the endoplasmic reticulum (ER) and, if not properly folded, are retained. An exception are glycosylphosphatidylinositol-anchored proteins (GPI-APs) which can leave the ER even when misfolded and are routed to the vacuole/lysosome for degradation by largely unknown mechanisms linked to post-ER quality control. Using yeast as model organism,we show that Gas1*, an ER-exported misfolded GPI-AP, is diverted from the secretory pathway to endosomes for transport to the vacuole. However, Gas1* is not sorted into endosomal intraluminal vesicles but internalizes directly from the vacuolar membrane.There, the vacuolar protease Pep4, but not any other known vacuolar protease, is required for Gas1* internalization. Our data reveal novel and unexpected mechanisms for invaginations from the vacuolar membrane.

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Three Distinct Types of Microautophagy Based on Membrane Dynamics and Molecular Machineries

Cited by 190 publications

References 50 publications

ER‐phagy: shaping up and destressing the endoplasmic reticulum

ER‐phagy: shaping up and destressing the endoplasmic reticulum

ESCRT machinery mediates selective microautophagy of endoplasmic reticulum

A post-ER degradation pathway that relies on protease-dependent internalization from the vacuolar membrane

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