Mitochondrial Dysfunction and Mitophagy in Parkinson’s Disease: From Mechanism to Therapy

CHCHD2 harboring the Parkinson’s disease-linked T61I mutation precipitates inside mitochondria and induces precipitation of wild-type CHCHD2

(2020) Tom Cornelissen et al.   HUMAN MOLECULAR GENETICS

Lysosome and Inflammatory Defects in GBA1 ‐Mutant Astrocytes Are Normalized by LRRK2 Inhibition

(2020) Anwesha Sanyal et al.   MOVEMENT DISORDERS

The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration

(2020) Anne-Laure Mahul-Mellier et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Deep phenotyping of peripheral tissue facilitates mechanistic disease stratification in sporadic Parkinson’s disease

(2020) Phillippa J Carling et al.   PROGRESS IN NEUROBIOLOGY

Visualizing and Modulating Mitophagy for Therapeutic Studies of Neurodegeneration

(2020) Hiroyuki Katayama et al.   CELL

Tollip coordinates Parkin‐dependent trafficking of mitochondrial‐derived vesicles

(2020) Thomas A Ryan et al.   EMBO JOURNAL

Loss of CHCHD2 and CHCHD10 activates OMA1 peptidase to disrupt mitochondrial cristae phenocopying patient mutations

(2020) Yi-Ting Liu et al.   HUMAN MOLECULAR GENETICS

Dynamic Regulation of Mitochondrial Import by the Ubiquitin System

(2020) Lilian Phu et al.   MOLECULAR CELL

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

(2020) Alban Ordureau et al.   MOLECULAR CELL

Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein

(2020) Eunna Chung et al.   Science Advances

Lysosomal perturbations in human dopaminergic neurons derived from induced pluripotent stem cells with PARK2 mutation

(2020) Justyna Okarmus et al.   Scientific Reports

A Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling

(2020) Kahori Shiba-Fukushima et al.   iScience

USP30 sets a trigger threshold for PINK1–PARKIN amplification of mitochondrial ubiquitylation

(2020) Emma V Rusilowicz-Jones et al.   Life Science Alliance

LRRK2 impairs PINK1/Parkin-dependent mitophagy via its kinase activity: pathologic insights into Parkinson’s disease

(2019) Fiona Bonello et al.   HUMAN MOLECULAR GENETICS

Pathogenic alpha-synuclein aggregates preferentially bind to mitochondria and affect cellular respiration

(2019) Xinhe Wang et al.   Acta Neuropathologica Communications

Probing Membrane Association of α-Synuclein Domains with VDAC Nanopore Reveals Unexpected Binding Pattern

(2019) Daniel Jacobs et al.   Scientific Reports

Structural and Functional Characterization of Ubiquitin Variant Inhibitors of USP15

(2019) Joan Teyra et al.   STRUCTURE

Cellular α-synuclein pathology is associated with bioenergetic dysfunction in Parkinson’s iPSC-derived dopamine neurons

(2019) Federico Zambon et al.   HUMAN MOLECULAR GENETICS

LRRK2 mutations impair depolarization-induced mitophagy through inhibition of mitochondrial accumulation of RAB10

(2019) Fieke Wauters et al.   Autophagy

Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1−/− mice

(2019) Diana Matheoud et al.   NATURE

Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes

(2019) Sarah H. Shahmoradian et al.   NATURE NEUROSCIENCE

Basal and Evoked Neurotransmitter Levels in Parkin, DJ-1, PINK1 and LRRK2 Knockout Rat Striatum

(2019) Rose B. Creed et al.   NEUROSCIENCE

Insights into ubiquitin chain architecture using Ub-clipping

(2019) Kirby N. Swatek et al.   NATURE

Mutations in CHCHD2 cause α-synuclein aggregation

(2019) Aya Ikeda et al.   HUMAN MOLECULAR GENETICS

The ADP/ATP translocase drives mitophagy independent of nucleotide exchange

(2019) Atsushi Hoshino et al.   NATURE

Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain

(2019) Steven M. Graves et al.   NATURE NEUROSCIENCE

Perturbations in RhoA signalling cause altered migration and impaired neuritogenesis in human iPSC-derived neural cells with PARK2 mutation

(2019) Helle Bogetofte et al.   NEUROBIOLOGY OF DISEASE

Loss of Parkin contributes to mitochondrial turnover and dopaminergic neuronal loss in aged mice

(2019) Sachiko Noda et al.   NEUROBIOLOGY OF DISEASE

LRRK2 inhibition prevents endolysosomal deficits seen in human Parkinson's disease

(2019) Emily M. Rocha et al.   NEUROBIOLOGY OF DISEASE

PPEF2 Opposes PINK1-Mediated Mitochondrial Quality Control by Dephosphorylating Ubiquitin

(2019) Christopher E. Wall et al.   Cell Reports

Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson’s models

(2018) Atossa Shaltouki et al.   ACTA NEUROPATHOLOGICA

PTENα Regulates Mitophagy and Maintains Mitochondrial Quality Control

(2018) Yuxin Yin et al.   Autophagy

Age- and disease-dependent increase of the mitophagy marker phospho-ubiquitin in normal aging and Lewy body disease

(2018) Xu Hou et al.   Autophagy

Somatic copy number gains of α-synuclein (SNCA) in Parkinson’s disease and multiple system atrophy brains

(2018) Katya Mokretar et al.   BRAIN

Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand

(2018) Thomas G. McWilliams et al.   Cell Metabolism

PTEN-L is a novel protein phosphatase for ubiquitin dephosphorylation to inhibit PINK1–Parkin-mediated mitophagy

(2018) Liming Wang et al.   CELL RESEARCH

Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance

(2018) Sarah Pickles et al.   CURRENT BIOLOGY

Dual role of USP30 in controlling basal pexophagy and mitophagy

(2018) Elena Marcassa et al.   EMBO REPORTS

Basal mitophagy is widespread inDrosophilabut minimally affected by loss of Pink1 or parkin

(2018) Juliette J. Lee et al.   JOURNAL OF CELL BIOLOGY

Systemic isradipine treatment diminishes calcium-dependent mitochondrial oxidant stress

(2018) Jaime N. Guzman et al.   JOURNAL OF CLINICAL INVESTIGATION

Mechanism of parkin activation by PINK1

(2018) Christina Gladkova et al.   NATURE

Building and decoding ubiquitin chains for mitophagy

(2018) J. Wade Harper et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Mitochondrial calcium imbalance in Parkinson’s disease

(2018) Marthe H.R. Ludtmann et al.   NEUROSCIENCE LETTERS

S-nitrosylation drives cell senescence and aging in mammals by controlling mitochondrial dynamics and mitophagy

(2018) Salvatore Rizza et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease

(2018) Marthe H. R. Ludtmann et al.   Nature Communications

AKT signalling selectively regulates PINK1 mitophagy in SHSY5Y cells and human iPSC-derived neurons

(2018) Marc P. M. Soutar et al.   Scientific Reports

The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson’s Disease

(2018) David C. Schöndorf et al.   Cell Reports

Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila

(2018) Tom Cornelissen et al.   eLife

Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy

(2018) Gian-Luca McLelland et al.   eLife

Mitochondrial Dysfunction and Mitophagy Defect Triggered by Heterozygous GBA Mutations

(2018) Hongyu Li et al.   Autophagy

Chemical Strategies for Activating PINK1, a Protein Kinase Mutated in Parkinson’s Disease

(2018) Olivia A Lambourne et al.   CHEMBIOCHEM

USP14 inhibition corrects an in vivo model of impaired mitophagy

(2018) Joy Chakraborty et al.   EMBO Molecular Medicine

Parkin and PINK1 mitigate STING-induced inflammation

(2018) Danielle A. Sliter et al.   NATURE

No Parkin Zone: Mitophagy without Parkin

(2018) Elodie Villa et al.   TRENDS IN CELL BIOLOGY

CHCHD2 accumulates in distressed mitochondria and facilitates oligomerization of CHCHD10

(2018) Xiaoping Huang et al.   HUMAN MOLECULAR GENETICS

Mitochondrial dysfunction and increased glycolysis in prodromal and early Parkinson's blood cells

(2018) Amy M. Smith et al.   MOVEMENT DISORDERS

A novel role for endothelial tetrahydrobiopterin in mitochondrial redox balance

(2017) Jade Bailey et al.   FREE RADICAL BIOLOGY AND MEDICINE

Vps35 in cooperation with LRRK2 regulates synaptic vesicle endocytosis through the endosomal pathway in Drosophila

(2017) Tsuyoshi Inoshita et al.   HUMAN MOLECULAR GENETICS

Quantitative proteomic analysis of Parkin substrates in Drosophila neurons

(2017) Aitor Martinez et al.   Molecular Neurodegeneration

Structure of PINK1 in complex with its substrate ubiquitin

(2017) Alexander F. Schubert et al.   NATURE

Mechanism and regulation of the Lys6-selective deubiquitinase USP30

(2017) Malte Gersch et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30

(2017) Yusuke Sato et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Genome-wide CRISPR screen for PARKIN regulators reveals transcriptional repression as a determinant of mitophagy

(2017) Christoph Potting et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Loss of Parkinson’s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c

(2017) Hongrui Meng et al.   Nature Communications

Mechanism and regulation of the Lys6-selective deubiquitinase USP30

(2017) Malte Gersch et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30

(2017) Yusuke Sato et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival

(2017) Yunjong Lee et al.   Cell Reports

S-Nitrosylation of PINK1 Attenuates PINK1/Parkin-Dependent Mitophagy in hiPSC-Based Parkinson’s Disease Models

(2017) Chang-Ki Oh et al.   Cell Reports

Functional Impairment in Miro Degradation and Mitophagy Is a Shared Feature in Familial and Sporadic Parkinson’s Disease

(2016) Chung-Han Hsieh et al.   Cell Stem Cell

The PINK1, synphilin-1 and SIAH-1 complex constitutes a novel mitophagy pathway

(2016) Raymonde Szargel et al.   HUMAN MOLECULAR GENETICS

mito-QC illuminates mitophagy and mitochondrial architecture in vivo

(2016) Thomas G. McWilliams et al.   JOURNAL OF CELL BIOLOGY

α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson’s disease

(2016) Roberto Di Maio et al.   Science Translational Medicine

Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease

(2016) Christian Dölle et al.   Nature Communications

Mitochondrial outer-membrane E3 ligase MUL1 ubiquitinates ULK1 and regulates selenite-induced mitophagy

(2015) Jie Li et al.   Autophagy

(Patho-)physiological relevance of PINK1-dependent ubiquitin phosphorylation

(2015) F. C. Fiesel et al.   EMBO REPORTS

F-box protein 7 mutations promote protein aggregation in mitochondria and inhibit mitophagy

(2015) Zhi Dong Zhou et al.   HUMAN MOLECULAR GENETICS

CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study

(2015) Manabu Funayama et al.   LANCET NEUROLOGY

Mechanism of phospho-ubiquitin-induced PARKIN activation

(2015) Tobias Wauer et al.   NATURE

USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria

(2015) Christian N. Cunningham et al.   NATURE CELL BIOLOGY

Parkinson's disease–associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes

(2015) Wenzhang Wang et al.   NATURE MEDICINE

A novel quantitative assay of mitophagy: Combining high content fluorescence microscopy and mitochondrial DNA load to quantify mitophagy and identify novel pharmacological tools against pathogenic heteroplasmic mtDNA

(2015) Alan Diot et al.   PHARMACOLOGICAL RESEARCH

Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers

(2014) Niccolò E. Mencacci et al.   BRAIN

Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis

(2014) T. Wauer et al.   EMBO JOURNAL

USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin

(2014) T. M. Durcan et al.   EMBO JOURNAL

Differential LRRK2 expression in the cortex, striatum, and substantia nigra in transgenic and nontransgenic rodents

(2014) Andrew B. West et al.   JOURNAL OF COMPARATIVE NEUROLOGY

A Regulatory Signaling Loop Comprising the PGAM5 Phosphatase and CK2 Controls Receptor-Mediated Mitophagy

(2014) Guo Chen et al.   MOLECULAR CELL

The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy

(2014) Baris Bingol et al.   NATURE

Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations

(2014) Vinay K. Godena et al.   Nature Communications

A Neo-Substrate that Amplifies Catalytic Activity of Parkinson’s-Disease-Related Kinase PINK1

(2013) Nicholas T. Hertz et al.   CELL

α-Synuclein and mitochondrial bioenergetics regulate tetrahydrobiopterin levels in a human dopaminergic model of Parkinson disease

(2013) Brent J. Ryan et al.   FREE RADICAL BIOLOGY AND MEDICINE

The Parkinson's disease–linked proteins Fbxo7 and Parkin interact to mediate mitophagy

(2013) Victoria S Burchell et al.   NATURE NEUROSCIENCE

The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo

(2013) E. S. Vincow et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Living on the edge with too many mouths to feed: Why dopamine neurons die

(2012) J. Paul Bolam et al.   MOVEMENT DISORDERS

A Sensitive and Quantitative Technique for Detecting Autophagic Events Based on Lysosomal Delivery

(2011) Hiroyuki Katayama et al.   CHEMISTRY & BIOLOGY

Vps35 Mediates Vesicle Transport between the Mitochondria and Peroxisomes

(2010) Emélie Braschi et al.   CURRENT BIOLOGY

PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin

(2010) Derek P. Narendra et al.   PLOS BIOLOGY

Proteomics Analysis Identifies Phosphorylation-dependent α-Synuclein Protein Interactions

(2008) Melinda A. McFarland et al.   MOLECULAR & CELLULAR PROTEOMICS