Global Landscape and Dynamics of Parkin and USP30-Dependent Ubiquitylomes in iNeurons during Mitophagic Signaling.

Molecular Cell
Alban OrdureauJ Wade Harper

Abstract

The ubiquitin ligase Parkin, protein kinase PINK1, USP30 deubiquitylase, and p97 segregase function together to regulate turnover of damaged mitochondria via mitophagy, but our mechanistic understanding in neurons is limited. Here, we combine induced neurons (iNeurons) derived from embryonic stem cells with quantitative proteomics to reveal the dynamics and specificity of Parkin-dependent ubiquitylation under endogenous expression conditions. Targets showing elevated ubiquitylation in USP30-/- iNeurons are concentrated in components of the mitochondrial translocon, and the ubiquitylation kinetics of the vast majority of Parkin targets are unaffected, correlating with a modest kinetic acceleration in accumulation of pS65-Ub and mitophagic flux upon mitochondrial depolarization without USP30. Basally, ubiquitylated translocon import substrates accumulate, suggesting a quality control function for USP30. p97 was dispensable for Parkin ligase activity in iNeurons. This work provides an unprecedented quantitative landscape of the Parkin-modified ubiquitylome in iNeurons and reveals the underlying specificity of central regulatory elements in the pathway.

Citations

Apr 17, 2020·Biological Chemistry·Verian Bader, Konstanze F Winklhofer
May 7, 2020·Frontiers in Cell and Developmental Biology·Ashley E Gonzalez, Xinnan Wang
Sep 24, 2020·International Journal of Molecular Sciences·Mafalda Escobar-Henriques, Vincent Anton
Jun 2, 2020·Frontiers in Cell and Developmental Biology·Liming WangHan-Ming Shen
Jul 9, 2020·Life Science Alliance·Emma V Rusilowicz-JonesMichael J Clague
Aug 5, 2020·Annual Review of Cell and Developmental Biology·Pawan Kishor Singh, Miratul M K Muqit
Oct 20, 2020·Frontiers in Cell and Developmental Biology·Mariana Joaquim, Mafalda Escobar-Henriques
Oct 22, 2020·Biomolecules·George VereAdan Pinto-Fernandez
Nov 30, 2020·FEBS Letters·Lena KrämerJohannes M Herrmann
Jan 9, 2021·Cell Death and Differentiation·Marlene F SchmidtGrant Dewson
Jan 14, 2021·The EMBO Journal·Mashun OnishiKoji Okamoto
Jan 24, 2021·Cell Death & Disease·Fatima Amer-SarsourAvraham Ashkenazi
Feb 2, 2021·Frontiers in Neuroscience·Helen ZhaoGabriel G Haddad
Nov 20, 2020·Biomolecules·Prasad SulkshaneMichael H Glickman
Oct 24, 2020·Nature Reviews. Molecular Cell Biology·Jiyao SongThomas Becker
Feb 5, 2021·Frontiers in Cell and Developmental Biology·Christina Doxaki, Konstantinos Palikaras
Mar 6, 2021·Molecular Psychiatry·Michele FrisonMichelangelo Campanella
Aug 26, 2020·Trends in Biochemical Sciences·Noboru Mizushima, Leon O Murphy
Dec 17, 2020·Trends in Biochemical Sciences·Ana Belen MalpartidaBrent J Ryan
Apr 2, 2021·The Journal of Cell Biology·Jacob A Culver, Malaiyalam Mariappan
Apr 5, 2021·Current Opinion in Chemical Biology·Kirandeep K Deol, Eric R Strieter
Apr 24, 2021·Cell Chemical Biology·Predrag JevtićMichael Rapé
Apr 24, 2021·Acta Physiologica·Hongke LuoNuo Sun
Jun 22, 2021·The EMBO Journal·Guillermo López-DoménechJosef T Kittler
Aug 1, 2021·Biochimica Et Biophysica Acta. General Subjects·Koji Yamano, Waka Kojima
Apr 17, 2020·Journal of the American Society for Mass Spectrometry·Kirandeep K DeolEric R Strieter
Aug 27, 2021·The Biochemical Journal·Fabian den BraveThomas Becker

❮ Previous
Next ❯

Methods Mentioned

BETA
size exclusion chromatography
immunoprecipitation
ubiquitination
co-immunoprecipitation
Protein Assay
transfection
genotyping
PCR
scraping
X-ray

Software Mentioned

Sequest
MetaMorph
ReAdW
MS
LBPro
Fiji
diGLY
Perseus
MultiStage Activation
TMT

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.