Peroxisome protein import deficiency causes heart failure in mouse and human
Hofhuis, J.; Tiburcy, M.; Hatmann, Y.; Bersch, K.; Wagdi, A.; Guiterrez-Gutierrez, O.; Solano, R.; Thiele, L.; Walper, M.; Goebel, M.; Huebner, W.; Berecic, B.; Casini, M.; Tirilomis, P.; Unger, A.; Lipstein, N.; Sossalla, S.; Huser, T.; Streckfuss-Boemeke, K.; Elkenani, M.; Toischer, K.; Kohlhaas, M.; Dudek, J.; Zimmermann, W.; Voigt, N.; Bruegmann, T.; Maack, C.; Cyganek, L.; Thoms, S.
Show abstract
Peroxisomes are ubiquitous cellular organelles with potentially vital roles in lipid and reactive oxygen metabolism. The metabolic demands of the heart are substantial; however, the contribution of peroxisomes to cardiac development, health, and their role in heart failure (HF) remain largely unexplored. We developed and examined a mouse and an engineered human myocardium (EHM) model with a deficiency in cardiac peroxisome biogenesis to investigate the role of peroxisomes in cardiac function and pathology. In the EHM, loss of peroxisome protein import and subsequent peroxisomal metabolic impairment trigger mitochondrial damage and compromise cellular respiration and energy production. Peroxisome dysfunction results in incoherent electrical conduction, defective Ca2+-handling, and ultimately presentation of a HF phenotype with pathological force generation. These phenotypes are mirrored in an orthogonal murine model system with defective cardiac peroxisome biogenesis. Preload-dependent deficits in force generation due to insufficient energy supply are eventually fatal. Thus, peroxisomes play an important role in sustaining normal heart operations. Vice versa, peroxisome maintenance is compromised in pressure overload-induced HF, establishing peroxisomes as potential modulators of pathology and targets of therapy.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Targeted glycophagy ATG8 therapy reverses diabetic heart disease in mice and in human engineered cardiac tissues 97%
- Tbx5 maintains atrial identity by regulating an atrial enhancer network 96%
- Glucocorticoid Receptor ablation promotes cardiac regeneration by hampering cardiomyocyte terminal differentiation 96%
Similar papers in this journal
- Mitochondrial CaMKII causes metabolic reprogramming, energetic insufficiency, and dilated cardiomyopathy 97%
- Mitochondrial fission process 1 (MTFP1) controls bioenergetic efficiency and prevents inflammatory cardiomyopathy and heart failure in mice 97%
- Nkx2-5 defines distinct scaffold and recruitment phases during formation of the cardiac Purkinje fiber network 97%
Similar papers in this journal
- The EMT transcription factor Snai1 maintains myocardial wall integrity by repressing intermediate filament gene expression 97%
- Crest maturation at the cardiomyocyte surface contributes to a new late postnatal development stage that controls the diastolic function of the adult heart 96%
- Contraction-induced endocardial id2b plays a dual role in regulating myocardial contractility and valve formation 96%
Similar papers in this journal
- Atf3 controls transitioning in female mitochondrial cardiomyopathy as identified by single-cell transcriptomics 98%
- Optogenetic quantification of source sink relationship in intact hearts to explain cardiac arrhythmia initiation and protection 96%
- GATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.