Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Takeda, Kazuhisa; Yoshida, Tomoko; Kikuchi, Sakura; Nagao, Koji; Kokubu, Aya; Pluskal, Tomáš; Villar‐Briones, Alejandro; Nakamura, Takahiro; Yanagida, Mitsuhiro

doi:10.1073/pnas.0911055107

Cited by 81 publications

(87 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If mitochondrial damage is massive, Parkin may trigger whole mitochondrial degradation by mitophagy. Such cooperation between the ubiquitin-proteasome system and mitophagy has also been observed in fission yeast; proteasome dysfunction causes mitophagy in G 0 phase to reduce the level of reactive oxygen species (58). Although more studies will be required, particularly using primary neurons, Parkin could be a key factor that regulates cellular homeostasis through mitochondrial turnover in both an autophagy-dependent and a proteasome-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Parkin Mediates Proteasome-dependent Protein Degradation and Rupture of the Outer Mitochondrial Membrane

Yoshii

Kishi

Ishihara

et al. 2011

Journal of Biological Chemistry

551

463

View full text Add to dashboard Cite

Upon mitochondrial depolarization, Parkin, a Parkinson disease-related E3 ubiquitin ligase, translocates from the cytosol to mitochondria and promotes their degradation by mitophagy, a selective type of autophagy. Here, we report that in addition to mitophagy, Parkin mediates proteasome-dependent degradation of outer membrane proteins such as Tom20, Tom40, Tom70, and Omp25 of depolarized mitochondria. By contrast, degradation of the inner membrane and matrix proteins largely depends on mitophagy. Furthermore, Parkin induces rupture of the outer membrane of depolarized mitochondria, which also depends on proteasomal activity. Upon induction of mitochondrial depolarization, proteasomes are recruited to mitochondria in the perinuclear region. Neither proteasome-dependent degradation of outer membrane proteins nor outer membrane rupture is required for mitophagy. These results suggest that Parkin regulates degradation of outer and inner mitochondrial membrane proteins differently through proteasome-and mitophagydependent pathways.Parkinson disease is a progressive neurodegenerative disease that is characterized by postural changes, resting tremor, muscle rigidity, and weakness (1, 2). These symptoms are mainly caused by loss of dopaminergic neurons in the substantia nigra, and mitochondrial dysfunction appears to be the primary pathogenic event. Indeed, many of the products of Parkinson disease-related genes such as ␣-synuclein/PARK1/4, PARKIN/ PARK2, PINK1/PARK6, DJ-I/PARK7, and OMI/HTRA2 are physically and functionally linked to mitochondria (3,4).Parkin is a RING domain-containing E3 ubiquitin ligase, and its mutation causes autosomal recessive juvenile Parkinson disease (5). Recent studies have revealed that Parkin is important for mitochondrial quality control through degradation of damaged mitochondria. Narendra et al. (6) first demonstrated that Parkin translocates from the cytosol to depolarized mitochondria and triggers elimination of these mitochondria by autophagy, which is known as mitophagy. Targeting of Parkin to mitochondria requires PTEN-induced putative kinase 1 (Pink1), 3 another Parkinson disease-associated gene product (7-14). Pink1 is an extremely unstable mitochondrial protein, but it is stabilized upon mitochondrial depolarization and subsequently recruits Parkin.Autophagy is a membrane-mediated intracellular degradation process. A portion of cytoplasm is first enclosed by the double-membraned autophagosome, and the autophagosome then fuses with a lysosome to degrade the enclosed materials. Although autophagy has been thought to be mainly non-selective, recent studies have revealed that the autophagosomal membrane can recognize some specific proteins and organelles. Parkin-mediated autophagy of damaged mitochondria is one of the best examples of selective autophagy. However, the precise role of Parkin in the induction of mitophagy has not been fully elucidated. To date, several mitochondrial proteins, voltage-dependent anion channel 1 (VDAC1) (8), mitofusin (a mitochondrial pro-fusion factor)...

show abstract

Section: Discussionmentioning

confidence: 99%

Parkin Mediates Proteasome-dependent Protein Degradation and Rupture of the Outer Mitochondrial Membrane

Yoshii

Kishi

Ishihara

et al. 2011

Journal of Biological Chemistry

551

463

View full text Add to dashboard Cite

show abstract

“…An interaction between Cut8 and the proteasome was subsequently demonstrated (11). Additional data showing that Cut8 is essential for nuclear localization is the recent finding that a reduction in Cut8 levels coincides with the altered localization of the proteasome from the nucleus to the cytoplasm upon the transition from vegetative proliferation to the G0/quiescent phase (22). Nuclear sequestration of the proteasome by Cut8 has also been shown to be critical for double-strand break repair (23).…”

mentioning

confidence: 87%

Implications for proteasome nuclear localization revealed by the structure of the nuclear proteasome tether protein Cut8

Takeda

Tonthat

Glover

et al. 2011

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

Self Cite

View full text Add to dashboard Cite

Degradation of nuclear proteins by the 26S proteasome is essential for cell viability. In yeast, the nuclear envelope protein Cut8 mediates nuclear proteasomal sequestration by an uncharacterized mechanism. Here we describe structures of Schizosaccharomyces pombe Cut8, which shows that it contains a unique, modular fold composed of an extended N-terminal, lysine-rich segment that when ubiquitinated binds the proteasome, a dimer domain followed by a six-helix bundle connected to a flexible C tail. The Cut8 six-helix bundle shows structural similarity to 14-3-3 phosphoprotein-binding domains, and binding assays show that this domain is necessary and sufficient for liposome and cholesterol binding. Moreover, specific mutations in the 14-3-3 regions corresponding to putative cholesterol recognition/interaction amino acid consensus motifs abrogate cholesterol binding. In vivo studies confirmed that the 14-3-3 region is necessary for Cut8 membrane localization and that dimerization is critical for its function. Thus, the data reveal the Cut8 organization at the nuclear envelope. Reconstruction of Cut8 evolution suggests that it was present in the last common ancestor of extant eukaryotes and accordingly that nuclear proteasomal sequestration is an ancestral eukaryotic feature. The importance of Cut8 for cell viability and its absence in humans suggests it as a possible target for the development of specific chemotherapeutics against invasive fungal infections.

show abstract

“…For example, autophagy is enhanced when proteasome activity is blocked by inhibitors (Pandey et al, 2007;Takeda et al, 2010). The induction of autophagy could compensate for insufficient proteasome activity, since up-regulation of autophagy was shown to protect cells from proteasome inhibition (Pandey et al, 2007).…”

Section: Ups and Selective Autophagymentioning

confidence: 99%

Genes for Plant Autophagy: Functions and Interactions

Kim

Kwon

Lee

et al. 2012

Molecules and Cells

View full text Add to dashboard Cite

Autophagy, or self-consuming of cytoplasmic constituents in a lytic compartment, plays a crucial role in nutrient recycling, development, cell homeostasis, and defense against pathogens and toxic products. Autophagy in plant cells uses a conserved machinery of core Autophagy-related (Atg) proteins. Recently, research on plant autophagy has been expanding and other components interacting with the core Atg proteins are being revealed. In addition, growing evidence suggests that autophagy communicates with other cellular pathways such as the ubiquitin-proteasome system, protein secretory pathway, and endocytic pathway. An increase in our understanding of plant autophagy will undoubtedly help test the hypothesized functions of plant autophagy in programmed cell death, vacuole biogenesis, and responses to biotic, abiotic, and nutritional stresses. In this review, we summarize recent progress on these topics and suggest topics for future research, after inspecting common phenotypes of current Arabidopsis atg mutants.

show abstract

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Cited by 81 publications

References 43 publications

Parkin Mediates Proteasome-dependent Protein Degradation and Rupture of the Outer Mitochondrial Membrane

Parkin Mediates Proteasome-dependent Protein Degradation and Rupture of the Outer Mitochondrial Membrane

Implications for proteasome nuclear localization revealed by the structure of the nuclear proteasome tether protein Cut8

Genes for Plant Autophagy: Functions and Interactions

Contact Info

Product

Resources

About