Mechanistic dissection of macro- and micronucleophagy

Otto, Florian Bo; Thumm, Michael

doi:10.1080/15548627.2020.1725402

Cited by 38 publications

(55 citation statements)

References 42 publications

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“…Atg8 accumulates at the necks of these invaginations, indicating the presence of a phagophore-related structure similar to the MIPA. In addition, micronucleophagy requires Atg11 and the autophagy receptor Atg39 (Otto and Thumm, 2020). Thus, micronucleophagy is mechanistically related to micropexophagy.…”

Section: Micronucleophagymentioning

confidence: 99%

“…Macroautophagy and microautophagy of the same organelle are often activated simultaneously, as seen for pexophagy, ER-phagy and nucleophagy in yeast (Monastryska et al, 2004;Schäfer et al, 2019;Otto and Thumm, 2020). The benefit of such parallel targeting is not obvious, especially as even the cargo receptors are sometimes the same (Farré et al, 2008;Otto and Thumm, 2020).…”

Section: Physiological Roles Of Microautophagymentioning

confidence: 99%

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Microautophagy – distinct molecular mechanisms handle cargoes of many sizes

Schuck

2020

Journal of Cell Science

252

180

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Autophagy is fundamental for cell and organismal health. Two types of autophagy are conserved in eukaryotes: macroautophagy and microautophagy. During macroautophagy, autophagosomes deliver cytoplasmic constituents to endosomes or lysosomes, whereas during microautophagy lytic organelles take up cytoplasm directly. While macroautophagy has been investigated extensively, microautophagy has received much less attention. Nonetheless, it has become clear that microautophagy has a broad range of functions in biosynthetic transport, metabolic adaptation, organelle remodeling and quality control. This Review discusses the selective and non-selective microautophagic processes known in yeast, plants and animals. Based on the molecular mechanisms for the uptake of microautophagic cargo into lytic organelles, I propose to distinguish between fission-type microautophagy, which depends on ESCRT proteins, and fusion-type microautophagy, which requires the core autophagy machinery and SNARE proteins. Many questions remain to be explored, but the functional versatility and mechanistic diversity of microautophagy are beginning to emerge.

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Section: Micronucleophagymentioning

confidence: 99%

Section: Physiological Roles Of Microautophagymentioning

confidence: 99%

Microautophagy – distinct molecular mechanisms handle cargoes of many sizes

Schuck

2020

Journal of Cell Science

252

180

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“…Nucleophagy occurs in both a macro- and micronucleophagic manner in the budding yeast Saccharomyces cerevisiae [ 4 , 5 ]. Designation of nuclear material for autophagic degradation is mediated by autophagic cargo receptor Atg39, independent of the nucleophagic mode [ 10 ]. Nucleophagy involves the formation of micronuclei, small parts of nuclear material that bud off of the main nucleus, which are then degraded by delivery to the vacuole.…”

Section: Introductionmentioning

confidence: 99%

“…PMN depends on the autophagic machinery [ 13 , 14 ]. Localisation of the autophagic machinery in PMN is reminiscent of the micropexophagic membrane apparatus (MIPA), required for micropexophagy in Komagataella phaffii (former Pichia pastoris ) [ 10 , 15 , 16 ]. Its localisation is mirrored by the ESCRT-III complex in micro-ER-phagy [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Many cargos are shared between the nucleophagic modes, implicating nucleophagy in regulation of the nuclear envelope and its domains, as well as nucleoplasmic content, including the nucleolus ( Figure 1 ) [ 5 , 14 ]. The nucleus vacuole junction (NVJ), a large compositionally unique membrane contact site between vacuolar membrane and nuclear envelope is an exclusive target of PMN [ 4 , 10 ]. Regulation of the NVJ by PMN has many implications towards its influence on lipid metabolism and both nuclear and vacuolar membrane composition.…”

Section: Introductionmentioning

confidence: 99%

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Nucleophagy—Implications for Microautophagy and Health

Otto

Thumm

2020

IJMS

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Nucleophagy, the selective subtype of autophagy that targets nuclear material for autophagic degradation, was not only shown to be a model system for the study of selective macroautophagy, but also for elucidating the role of the core autophagic machinery within microautophagy. Nucleophagy also emerged as a system associated with a variety of disease conditions including cancer, neurodegeneration and ageing. Nucleophagic processes are part of natural cell development, but also act as a response to various stress conditions. Upon releasing small portions of nuclear material, micronuclei, the autophagic machinery transfers these micronuclei to the vacuole for subsequent degradation. Despite sharing many cargos and requiring the core autophagic machinery, recent investigations revealed the aspects that set macro- and micronucleophagy apart. Central to the discrepancies found between macro- and micronucleophagy is the nucleus vacuole junction, a large membrane contact site formed between nucleus and vacuole. Exclusion of nuclear pore complexes from the junction and its exclusive degradation by micronucleophagy reveal compositional differences in cargo. Regarding their shared reliance on the core autophagic machinery, micronucleophagy does not involve normal autophagosome biogenesis observed for macronucleophagy, but instead maintains a unique role in overall microautophagy, with the autophagic machinery accumulating at the neck of budding vesicles.

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Autophagy as a caretaker of nuclear integrity

Boyle,

Wilfling

2023

FEBS Letters

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Due to their essential functions, dysregulation of nuclear pore complexes (NPCs) is strongly associated with numerous human diseases, including neurodegeneration and cancer[1]. On a cellular level, longevity of scaffold nucleoporins in post‐mitotic cells of both C. elegans and mammals renders them vulnerable to age‐related damage, which is associated with an increase in pore leakiness and accumulation of intranuclear aggregates in rat brain cells[2–4]. Thus, understanding the mechanisms which underpin the homeostasis of this complex, as well as other nuclear proteins, is essential. In this review, autophagy‐mediated degradation pathways governing nuclear components in yeast will be discussed, with a particular focus on NPCs. Furthermore, the various nuclear degradation mechanisms identified thus far in diverse eukaryotes will also be highlighted.This article is protected by copyright. All rights reserved.

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Mechanistic dissection of macro- and micronucleophagy

Cited by 38 publications

References 42 publications

Microautophagy – distinct molecular mechanisms handle cargoes of many sizes

Microautophagy – distinct molecular mechanisms handle cargoes of many sizes

Nucleophagy—Implications for Microautophagy and Health

Autophagy as a caretaker of nuclear integrity

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