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PARL mediates Smac proteolytic maturation in mitochondria to promote apoptosis

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What this work says

Outgoing claims: the papers this work cites, builds on, or argues with.

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An improved workflow for quantitative N‐terminal charge‐based fractional diagonal chromatography (ChaFRADIC) to study proteolytic events in Arabidopsis thaliana

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Functional cooperation of the mitochondrial processing peptidase subunits

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Bi‐allelic CLPB mutations cause cataract, renal cysts, nephrocalcinosis and 3‐methylglutaconic aciduria, a novel disorder of mitochondrial protein disaggregation

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CLPB Mutations Cause 3-Methylglutaconic Aciduria, Progressive Brain Atrophy, Intellectual Disability, Congenital Neutropenia, Cataracts, Movement Disorder

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CLPB Variants Associated with Autosomal-Recessive Mitochondrial Disorder with Cataract, Neutropenia, Epilepsy, and Methylglutaconic Aciduria

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Processing of mitochondrial presequences

inferredcites →https://doi.org/10.1016/j.bbamem.2009.05.004openalex-snapshot

Cardiolipin acts as a mitochondrial signalling platform to launch apoptosis

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Mitochondrial Rhomboid PARL Regulates Cytochrome c Release during Apoptosis via OPA1-Dependent Cristae Remodeling

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OPA1 Controls Apoptotic Cristae Remodeling Independently from Mitochondrial Fusion

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The Mitochondrial Phosphatase PGAM5 Functions at the Convergence Point of Multiple Necrotic Death Pathways

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Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity

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Regulation of Skeletal Muscle Oxidative Capacity and Insulin Signaling by the Mitochondrial Rhomboid Protease PARL

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Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure

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IAP antagonists: promising candidates for cancer therapy

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Systematic and quantitative comparison of digest efficiency and specificity reveals the impact of trypsin quality on MS-based proteomics

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

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Mitofusins, from Mitochondria to Metabolism

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Mitochondrial Dynamics and Metabolic Regulation

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Cells lacking Pcp1p/Ugo2p, a rhomboid-like protease required for Mgm1p processing, lose mtDNA and mitochondrial structure in a Dnm1p-dependent manner, but remain competent for mitochondrial fusion

inferredcites →https://doi.org/10.1016/s0092-8674(00)00008-8openalex-snapshot

Smac, a Mitochondrial Protein that Promotes Cytochrome c–Dependent Caspase Activation by Eliminating IAP Inhibition

inferredcites →https://doi.org/10.1016/s0092-8674(00)00009-xopenalex-snapshot

Identification of DIABLO, a Mammalian Protein that Promotes Apoptosis by Binding to and Antagonizing IAP Proteins

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Stop and Go Extraction Tips for Matrix-Assisted Laser Desorption/Ionization, Nanoelectrospray, and LC/MS Sample Pretreatment in Proteomics

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Undesirable Charge-Enhancement of Isobaric Tagged Phosphopeptides Leads to Reduced Identification Efficiency

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Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment

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Novel Highly Sensitive, Specific, and Straightforward Strategy for Comprehensive N-Terminal Proteomics Reveals Unknown Substrates of the Mitochondrial Peptidase Icp55

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Structural and biochemical basis of apoptotic activation by Smac/DIABLO

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XIAP, the guardian angel

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Mitochondrial membrane remodelling regulated by a conserved rhomboid protease

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Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons

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XIAP discriminates between type I and type II FAS-induced apoptosis

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MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification

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Mutations in TTC19 cause mitochondrial complex III deficiency and neurological impairment in humans and flies

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New roles for mitochondrial proteases in health, ageing and disease

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IAP proteins: blocking the road to death's door

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Elevated XIAP expression alone does not confer chemoresistance

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Regulation of mitochondrial morphology through proteolytic cleavage of OPA1

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Significance analysis of microarrays applied to the ionizing radiation response

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Activation of mitochondrial protease OMA1 by Bax and Bak promotes cytochrome c release during apoptosis

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StarD7 Mediates the Intracellular Trafficking of Phosphatidylcholine to Mitochondria

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Rhomboid Protease PARL Mediates the Mitochondrial Membrane Potential Loss-induced Cleavage of PGAM5

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Processing of Mgm1 by the Rhomboid-type Protease Pcp1 Is Required for Maintenance of Mitochondrial Morphology and of Mitochondrial DNA

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OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L

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Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage

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Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells

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Regulation of OPA1 processing and mitochondrial fusion by m -AAA protease isoenzymes and OMA1

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Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL

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The i -AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission

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Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria

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Mature DIABLO/Smac Is Produced by the IMP Protease Complex on the Mitochondrial Inner Membrane

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OPA1 Processing Reconstituted in Yeast Depends on the Subunit Composition of them-AAA Protease in Mitochondria

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Functional alteration of PARL contributes to mitochondrial dysregulation in Parkinson's disease

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BV6, an IAP Antagonist, Activates Apoptosis and Enhances Radiosensitization of Non-small Cell Lung Carcinoma In Vitro

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Matplotlib: A 2D Graphics Environment

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PINK1 Loss-of-Function Mutations Affect Mitochondrial Complex I Activity via NdufA10 Ubiquinone Uncoupling

inferredcites →https://doi.org/10.1128/mcb.22.10.3509-3517.2002openalex-snapshot

Generation and Characterization of Smac/DIABLO-Deficient Mice

inferredcites →https://doi.org/10.1136/jmedgenet-2014-102952openalex-snapshot

Disruption of CLPB is associated with congenital microcephaly, severe encephalopathy and 3-methylglutaconic aciduria

inferredcites →https://doi.org/10.1146/annurev-genet-110410-132529openalex-snapshot

Fusion and Fission: Interlinked Processes Critical for Mitochondrial Health

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Mito-Morphosis: Mitochondrial Fusion, Fission, and Cristae Remodeling as Key Mediators of Cellular Function

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XIAP targeting sensitizes Hodgkin lymphoma cells for cytolytic T-cell attack

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In silico prediction of protein-protein interactions in human macrophages

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PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin

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Disaggregases, molecular chaperones that resolubilize protein aggregates

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SMAC Mimetic BV6 Enables Sensitization of Resistant Tumor Cells but also Affects Cytokine-Induced Killer (CIK) Cells: A Potential Challenge for Combination Therapy

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Haploinsufficiency for Stard7 Is Associated with Enhanced Allergic Responses in Lung and Skin

What points at this work

Incoming claims: where this work appears in other papers’ reference lists and arguments.

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Human CLPB forms ATP-dependent complexes in the mitochondrial intermembrane space

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Edaravone combined with dexamethasone exhibits synergic effects on attenuating smoke-induced inhalation lung injury in rats

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Genome-wide Survival Study Identifies PARL as a Novel Locus for Clinical Progression and Neurodegeneration in Alzheimer’s Disease

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PGAM5 promotes RIPK1-PANoptosome activity by phosphorylating and activating RIPK1 to mediate PANoptosis after subarachnoid hemorrhage in rats

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PGAM5 aggravated doxorubicin-induced cardiotoxicity by disturbing mitochondrial dynamics and exacerbating cardiomyocytes apoptosis

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Cleavage of mitochondrial homeostasis regulator PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state

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Mechanism-based traps enable protease and hydrolase substrate discovery

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Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases

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A C-terminal glutamine recognition mechanism revealed by E3 ligase TRIM7 structures

inferred← citeshttps://doi.org/10.1038/s41596-024-01006-xopenalex-snapshot

Capturing acyl–enzyme intermediates with genetically encoded 2,3-diaminopropionic acid for hydrolase substrate identification

inferred← citeshttps://doi.org/10.1038/s41598-017-09205-1openalex-snapshot

Identification of the N-terminal transmembrane domain of StarD7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer

inferred← citeshttps://doi.org/10.1038/s41598-018-31154-6openalex-snapshot

Instant Clue: A Software Suite for Interactive Data Visualization and Analysis

inferred← citeshttps://doi.org/10.1038/s41598-020-74311-6openalex-snapshot

ATP synthase modulation leads to an increase of spare respiratory capacity in HPV associated cancers

inferred← citeshttps://doi.org/10.1038/s41598-025-28183-3openalex-snapshot

Proteomics analysis reveals progesterone receptor induced mitochondria-mediated apoptosis in breast cancer cells

inferred← citeshttps://doi.org/10.1038/s42003-023-05703-3openalex-snapshot

The mitochondrial protease PARL is required for spermatogenesis

inferred← citeshttps://doi.org/10.1038/s44318-025-00375-7openalex-snapshot

Reprograming of the ubiquitin ligase Ubr1 by intrinsically disordered Roq1 through cooperating multifunctional motifs

inferred← citeshttps://doi.org/10.1073/pnas.1811938116openalex-snapshot

PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome

inferred← citeshttps://doi.org/10.1074/mcp.ra120.002082openalex-snapshot

The Mouse Heart Mitochondria N Terminome Provides Insights into ClpXP-Mediated Proteolysis

inferred← citeshttps://doi.org/10.1074/mcp.tir119.001560openalex-snapshot

Sensitive Determination of Proteolytic Proteoforms in Limited Microscale Proteome Samples

inferred← citeshttps://doi.org/10.1080/10985549.2025.2566671openalex-snapshot

From Biogenesis to Breakdown: How Protein Biogenesis and Quality Control Failures Drive Mitochondrial Disease

inferred← citeshttps://doi.org/10.1083/jcb.201708191openalex-snapshot

Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling

inferred← citeshttps://doi.org/10.1083/jcb.202305087openalex-snapshot

CLPB disaggregase dysfunction impacts the functional integrity of the proteolytic SPY complex

inferred← citeshttps://doi.org/10.1089/ars.2022.0124openalex-snapshot

Molecular Determinants of Mitochondrial Shape and Function and Their Role in Glaucoma

inferred← citeshttps://doi.org/10.1093/jb/mvad106openalex-snapshot

Mitochondrial quality control via organelle and protein degradation

inferred← citeshttps://doi.org/10.1093/jb/mvy077openalex-snapshot

Cleaved PGAM5 is released from mitochondria depending on proteasome-mediated rupture of the outer mitochondrial membrane during mitophagy

inferred← citeshttps://doi.org/10.1093/jb/mvz069openalex-snapshot

PINK1 import regulation at a crossroad of mitochondrial fate: the molecular mechanisms of PINK1 import

inferred← citeshttps://doi.org/10.1093/narcan/zcaa028openalex-snapshot

DDX5 resolves R-loops at DNA double-strand breaks to promote DNA repair and avoid chromosomal deletions

inferred← citeshttps://doi.org/10.1098/rsob.210002openalex-snapshot

The mitochondrial intermembrane space: the most constricted mitochondrial sub-compartment with the largest variety of protein import pathways

inferred← citeshttps://doi.org/10.1101/2021.01.06.425502openalex-snapshot

Barth syndrome cellular models have dysregulated respiratory chain complex I and mitochondrial quality control due to abnormal cardiolipin

inferred← citeshttps://doi.org/10.1101/2021.11.19.469224openalex-snapshot

Cleavage of PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state

inferred← citeshttps://doi.org/10.1101/2022.03.10.483744openalex-snapshot

Structural and Functional Insights into the Action Mode of A Mitochondrial AAA+ Disaggregase CLPB

inferred← citeshttps://doi.org/10.1101/2022.10.28.514188openalex-snapshot

Structural and Functional insights into the action mode of a Mitochondrial AAA+ Disaggregase CLPB

inferred← citeshttps://doi.org/10.1101/2025.03.06.641096openalex-snapshot

Omics analysis reveals striking effects of progesterone receptor on mitochondria and mitochondria-mediated apoptosis independent of caspases in Breast Cancer cells

inferred← citeshttps://doi.org/10.1101/2025.04.12.648505openalex-snapshot

The tumour suppressor LACTB remodels mitochondria to promote cytochrome c release and apoptosis

inferred← citeshttps://doi.org/10.1101/cshperspect.a033936openalex-snapshot

Mitochondrial Proteolysis and Metabolic Control

inferred← citeshttps://doi.org/10.1111/febs.14186openalex-snapshot

Bax, Bak and beyond — mitochondrial performance in apoptosis

inferred← citeshttps://doi.org/10.1113/jp287635openalex-snapshot

Mitochondrial proteostasis and cellular health: insights from chaperones and autophagy

inferred← citeshttps://doi.org/10.1126/sciadv.adx7809openalex-snapshot

The tumor suppressor LACTB remodels mitochondria to promote cytochrome c release and apoptosis

inferred← citeshttps://doi.org/10.1128/jvi.01212-22openalex-snapshot

Pattern Recognition Receptors of Nucleic Acids Can Cause Sublethal Activation of the Mitochondrial Apoptosis Pathway during Viral Infection

inferred← citeshttps://doi.org/10.1146/annurev-biochem-062917-012739openalex-snapshot

Mitochondrial Proteases: Multifaceted Regulators of Mitochondrial Plasticity

inferred← citeshttps://doi.org/10.1152/physrev.00058.2021openalex-snapshot

Mitochondria in health, disease, and aging

inferred← citeshttps://doi.org/10.1158/1535-7163.22522425openalex-snapshot

Supplementary video S1 from Enhancing Proteotoxic Stress in Leiomyosarcoma Cells Triggers Mitochondrial Dysfunctions, Cell Death, and Antitumor Activity in vivo

inferred← citeshttps://doi.org/10.1158/1535-7163.c.6543375openalex-snapshot

Data from Enhancing Proteotoxic Stress in Leiomyosarcoma Cells Triggers Mitochondrial Dysfunctions, Cell Death, and Antitumor Activity in vivo

inferred← citeshttps://doi.org/10.1158/1535-7163.c.6543375.v1openalex-snapshot

Data from Enhancing Proteotoxic Stress in Leiomyosarcoma Cells Triggers Mitochondrial Dysfunctions, Cell Death, and Antitumor Activity in vivo

inferred← citeshttps://doi.org/10.1158/1535-7163.mct-20-0521openalex-snapshot

Enhancing Proteotoxic Stress in Leiomyosarcoma Cells Triggers Mitochondrial Dysfunctions, Cell Death, and Antitumor Activity in vivo

inferred← citeshttps://doi.org/10.1159/000491730openalex-snapshot

Regulation of Apoptosis and Radiation Sensitization in Lung Cancer Cells via the Sirt1/NF-κB/Smac Pathway

inferred← citeshttps://doi.org/10.1186/s12915-017-0470-7openalex-snapshot

PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol

inferred← citeshttps://doi.org/10.1242/jcs.217745openalex-snapshot

Intramembrane proteolysis at a glance: from signalling to protein degradation

inferred← citeshttps://doi.org/10.1371/journal.pbio.3001987openalex-snapshot

Comprehensive structural characterization of the human AAA+ disaggregase CLPB in the apo- and substrate-bound states reveals a unique mode of action driven by oligomerization

inferred← citeshttps://doi.org/10.14411/eje.2022.035openalex-snapshot

Mitochondrial genomes of two wild silkmoths, Samia watsoni and Samia wangi (Lepidoptera: Saturniidae), and their phylogenetic implications

inferred← citeshttps://doi.org/10.15252/embj.201797909openalex-snapshot

PARL partitions the lipid transfer protein STARD7 between the cytosol and mitochondria

inferred← citeshttps://doi.org/10.15252/embj.201898993openalex-snapshot

Shuttle mission in the mitochondrial intermembrane space

inferred← citeshttps://doi.org/10.15252/embj.2019102922openalex-snapshot

Bacterial rhomboid proteases mediate quality control of orphan membrane proteins

inferred← citeshttps://doi.org/10.15252/embj.2019102935openalex-snapshot

Rhomboid intramembrane protease YqgP licenses bacterial membrane protein quality control as adaptor of FtsH AAA protease

inferred← citeshttps://doi.org/10.18632/oncotarget.26140openalex-snapshot

Phospholipidation of nuclear proteins by the human papillomavirus E6 oncoprotein: implication in carcinogenesis

inferred← citeshttps://doi.org/10.26508/lsa.202201413openalex-snapshot

FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration

inferred← citeshttps://doi.org/10.30574/wjarr.2023.17.1.1442openalex-snapshot

Intermembrane rhomboid protease activity of Rothia mucilaginosa

inferred← citeshttps://doi.org/10.3389/fcell.2023.1244313openalex-snapshot

Unveiling the potential of mitochondrial dynamics as a therapeutic strategy for acute kidney injury

inferred← citeshttps://doi.org/10.3389/fmolb.2017.00060openalex-snapshot

Hsp78 (78 kDa Heat Shock Protein), a Representative AAA Family Member Found in the Mitochondrial Matrix of Saccharomyces cerevisiae

inferred← citeshttps://doi.org/10.3389/fpls.2022.824080openalex-snapshot

Protein Processing in Plant Mitochondria Compared to Yeast and Mammals

inferred← citeshttps://doi.org/10.3389/fpls.2022.837528openalex-snapshot

Recent Advances in Understanding the Structural and Functional Evolution of FtsH Proteases

inferred← citeshttps://doi.org/10.3390/biomedicines7040082openalex-snapshot

Cyst Reduction in a Polycystic Kidney Disease Drosophila Model Using Smac Mimics

inferred← citeshttps://doi.org/10.3390/cancers13092020openalex-snapshot

Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets

inferred← citeshttps://doi.org/10.3390/cells10030537openalex-snapshot

Cell Death and Inflammation: The Role of Mitochondria in Health and Disease

inferred← citeshttps://doi.org/10.3390/ijms23031297openalex-snapshot

Mitochondrial Processing Peptidases—Structure, Function and the Role in Human Diseases

inferred← citeshttps://doi.org/10.3390/ijms23031320openalex-snapshot

The Mitochondrial PHB2/OMA1/DELE1 Pathway Cooperates with Endoplasmic Reticulum Stress to Facilitate the Response to Chemotherapeutics in Ovarian Cancer

inferred← citeshttps://doi.org/10.3390/microorganisms10010114openalex-snapshot

Brucella abortus Encodes an Active Rhomboid Protease: Proteome Response after Rhomboid Gene Deletion

inferred← citeshttps://doi.org/10.3390/microorganisms13092139openalex-snapshot

Mechanistic Insights into Eimeria tenella-Induced Host Cell Apoptosis Through Modulation of the Mitochondrial Permeability Transition Pore

inferred← citeshttps://doi.org/10.3390/microorganisms7070195openalex-snapshot

Dynamic Gene Network Analysis of Caco-2 Cell Response to Shiga Toxin-Producing Escherichia coli-Associated Hemolytic–Uremic Syndrome

inferred← citeshttps://doi.org/10.3892/mmr.2020.11173openalex-snapshot

Mild microwave ablation combined with HSP90 and TGF‑β1 inhibitors enhances the therapeutic effect on osteosarcoma

inferred← citeshttps://doi.org/10.64898/2026.02.13.705862openalex-snapshot

Cytoplasmic mRNA granules regulate cell fate decisions during PINK1/Parkin mitophagy

inferred← citeshttps://doi.org/10.7150/ijbs.33787openalex-snapshot

Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma

inferred← citeshttps://doi.org/10.7554/elife.112857openalex-snapshot

HAX1 drives assembly and activation of the mitochondrial intermembrane space chaperone CLPB

inferred← citeshttps://doi.org/10.7554/elife.112857.1openalex-snapshot

HAX1 drives assembly and activation of the mitochondrial intermembrane space chaperone CLPB

inferred← citeshttps://doi.org/10.7554/elife.55279openalex-snapshot

Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations

inferred← citeshttps://doi.org/10.7554/elife.84710openalex-snapshot

Mitochondrial defects caused by PARL deficiency lead to arrested spermatogenesis and ferroptosis

inferred← citeshttps://doi.org/10.7939/r3-hht2-ek58openalex-snapshot

Characterization of PARL-Mediated Intramembrane Proteolysis

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