ArticleCancers2021
The Mitochondrial Protease LonP1 Promotes Proteasome Inhibitor Resistance in Multiple Myeloma.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- A selective inhibitor reveals roles for LONP1 in mitochondrial proteostasis and OXPHOS dependencies.Life science alliance · 2026Article
- Reprogramming Mitochondrial Adaptation: LONP1 at the Crossroads of Proteostasis, Metabolism, and Disease.Antioxidants (Basel, Switzerland) · 2026Review
- Intracellular Activation of Dual-Pharmacophore Artezomib Enhances Selective Cytotoxicity in Hematologic Malignancies.Journal of medicinal chemistry · 2026Article
- Structural Analysis of Human LonP1 Protease Bound with the Native Substrate.Life (Basel, Switzerland) · 2026Article
- Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1.The Journal of clinical investigation · 2026Article
- Lessons in longevity from blood stem cells under protein stress.Trends in cell biology · 2026Review
- Gene Expression Profiling Identifies CAV1, CD44, and TFRC as Potential Diagnostic Markers and Therapeutic Targets for Multiple Myeloma.Cell biochemistry and biophysics · 2025Article
- LONP1 facilitates pulmonary artery smooth muscle cell glycolytic reprogramming by degrading MPC1 in pulmonary hypertension.Clinical science (London, England : 1979) · 2025Article
- Dual targeting of the mitochondrial Lon peptidase 1 and the chymotrypsin-like proteasome activity as a potential therapeutic strategy in malignant astrocytoma models.Pharmacological research · 2025Article
- Modulation of Lonp1 Activity by Small Compounds.Biomolecules · 2025Review
- Multiple myeloma inhibitory effects of natural compounds: enhancement through nanoparticle carriers.Frontiers in pharmacology · 2025Review
- A bird's eye view of mitochondrial unfolded protein response in cancer: mechanisms, progression and further applications.Cell death & disease · 2024Review
- Different Strategies to Overcome Resistance to Proteasome Inhibitors-A Summary 20 Years after Their Introduction.International journal of molecular sciences · 2024Review
- Coordinated DNA polymerization by Polγ and the region of LonP1 regulated proteolysis.Nucleic acids research · 2024Article
- The synthetic oleanane triterpenoid CDDO-2P-Im binds GRP78/BiP to induce unfolded protein response-mediated apoptosis in myeloma.Molecular oncology · 2023Article
- Metabolic Alterations in Multiple Myeloma: From Oncogenesis to Proteasome Inhibitor Resistance.Cancers · 2023Review
- Proteasome Inhibitors Silence Oncogenes in Multiple Myeloma through Localized Histone Deacetylase 3 (HDAC3) Stabilization and Chromatin Condensation.Cancer research communications · 2022Article
- Inhibition of mitochondrial LonP1 protease by allosteric blockade of ATP binding and hydrolysis via CDDO and its derivatives.The Journal of biological chemistry · 2022Article
- Insight into the mitochondrial unfolded protein response and cancer: opportunities and challenges.Cell & bioscience · 2022Review
- Imaging-Based Screening of Deubiquitinating Proteases Identifies Otubain-1 as a Stabilizer of c-MYC.Cancers · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple myeloma and its precursor plasma cell dyscrasias affect 3% of the elderly population in the US. Proteasome inhibitors are an essential part of several standard drug combinations used to treat this incurable cancer. These drugs interfere with the main pathway of protein degradation and lead to the accumulation of damaged proteins inside cells. Despite promising initial responses, multiple myeloma cells eventually become drug resistant in most patients. The biology behind relapsed/refractory multiple myeloma is complex and poorly understood. Several studies provide evidence that in addition to the proteasome, mitochondrial proteases can also contribute to protein quality control outside of mitochondria. We therefore hypothesized that mitochondrial proteases might counterbalance protein degradation in cancer cells treated with proteasome inhibitors. Using clinical and experimental data, we found that overexpression of the mitochondrial matrix protease LonP1 (Lon Peptidase 1) reduces the efficacy of proteasome inhibitors. Some proteasome inhibitors partially crossinhibit LonP1. However, we show that the resistance effect of LonP1 also occurs when using drugs that do not block this protease, suggesting that LonP1 can compensate for loss of proteasome activity. These results indicate that targeting both the proteasome and mitochondrial proteases such as LonP1 could be beneficial for treatment of multiple myeloma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.