ArticlePloS one2020
Perm1 regulates cardiac energetics as a downstream target of the histone methyltransferase Smyd1.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- PERM1-An Emerging Transcriptional Regulator of Mitochondrial Biogenesis: A Systematic Review.Genes · 2024Pooled it
- PERM1 Gene Therapy Prevents Pressure Overload-induced Heart Failure Through a Sarcomere-Mitochondria Energetic Microdomain.Research square · 2026Article
- Perm1 enhances Nrf2-driven antioxidant defense through Keap1 oxidation during myocardial ischemia/reperfusion injury.JCI insight · 2026Article
- PERM1 Is Selectively Restored in Left Ventricular Assist Device-Mediated Myocardial Recovery in Heart Failure.Journal of the American Heart Association · 2026Article
- Regulation of mitochondrial biogenesis and energy metabolism in the heart.Chinese medical journal · 2026Review
- Article
- Analysis of systolic cardiac function in PERM1-knockout mice using large cohorts of animals.Scientific reports · 2026Article
- Chromatin structural gene expression stratifies cardiac cell populations in health and disease.Epigenetics · 2025Article
- PERM1 Gene Delivery via AAV Prevents Heart Failure in a Mouse Model of Pressure Overload.bioRxiv : the preprint server for biology · 2025Article
- PERM1 regulates mitochondrial energetics through O-GlcNAcylation in the heart.Journal of molecular and cellular cardiology · 2025Article
- Direct mitochondrial import of lactate supports resilient carbohydrate oxidation.bioRxiv : the preprint server for biology · 2024Article
- SMYD1 modulates the proliferation of multipotent cardiac progenitor cells derived from human pluripotent stem cells during myocardial differentiation through GSK3β/β-catenin&ERK signaling.Stem cell research & therapy · 2024Article
- Adeno-associated virus-mediated gene delivery ofAmerican journal of physiology. Heart and circulatory physiology · 2024Article
- Sex difference in human diseases: mechanistic insights and clinical implications.Signal transduction and targeted therapy · 2024Review
- CHD4 and SMYD1 repress common transcriptional programs in the developing heart.Development (Cambridge, England) · 2024Article
- Cardiac maturation.Journal of molecular and cellular cardiology · 2024Review
- Expression of Smyd1b_tv1 by Alternative Splicing in Cardiac Muscle is Critical for Sarcomere Organization in Cardiomyocytes and Heart Function.Molecular and cellular biology · 2024Article
- Musashi-2 causes cardiac hypertrophy and heart failure by inducing mitochondrial dysfunction through destabilizing Cluh and Smyd1 mRNA.Basic research in cardiology · 2023Article
- Review
- Sex and diet-dependent gene alterations in human and rat brains with a history of nicotine exposure.Frontiers in psychiatry · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
Abstract
The transcriptional regulatory machinery in mitochondrial bioenergetics is complex and is still not completely understood. We previously demonstrated that the histone methyltransferase Smyd1 regulates mitochondrial energetics. Here, we identified Perm1 (PPARGC-1 and ESRR-induced regulator, muscle specific 1) as a downstream target of Smyd1 through RNA-seq. Chromatin immunoprecipitation assay showed that Smyd1 directly interacts with the promoter of Perm1 in the mouse heart, and this interaction was significantly reduced in mouse hearts failing due to pressure overload for 4 weeks, where Perm1 was downregulated (24.4 ± 5.9% of sham, p<0.05). Similarly, the Perm1 protein level was significantly decreased in patients with advanced heart failure (55.2 ± 13.1% of donors, p<0.05). Phenylephrine (PE)-induced hypertrophic stress in cardiomyocytes also led to downregulation of Perm1 (55.7 ± 5.7% of control, p<0.05), and adenovirus-mediated overexpression of Perm1 rescued PE-induced downregulation of estrogen-related receptor alpha (ERRα), a key transcriptional regulator of mitochondrial energetics, and its target gene, Ndufv1 (Complex I). Pathway enrichment analysis of cardiomyocytes in which Perm1 was knocked-down by siRNA (siPerm1), revealed that the most downregulated pathway was metabolism. Cell stress tests using the Seahorse XF analyzer showed that basal respiration and ATP production were significantly reduced in siPerm1 cardiomyocytes (40.7% and 23.6% of scrambled-siRNA, respectively, both p<0.05). Luciferase reporter gene assay further revealed that Perm1 dose-dependently increased the promoter activity of the ERRα gene and known target of ERRα, Ndufv1 (Complex I). Overall, our study demonstrates that Perm1 is an essential regulator of cardiac energetics through ERRα, as part of the Smyd1 regulatory network.
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.