ArticleAutophagy2022
Perinatal versus adult loss of ULK1 and ULK2 distinctly influences cardiac autophagy and function.
Article in Autophagy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
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- Unveiling the Complexities: Exploring Mechanisms of Anthracyclineinduced Cardiotoxicity.Current cardiology reviews · 2025Review
- Cuproptosis-related Gene Signatures and Immunological Characterization in Sepsis-associated Acute Lung Injury.Combinatorial chemistry & high throughput screening · 2025Article
- The multifaceted role of autophagy and mitophagy in cardiovascular health and disease.Autophagy reports · 2025Review
- Comparative analysis of two independent Myh6-Cre transgenic mouse lines.Journal of molecular and cellular cardiology plus · 2024Article
- Allelic heterogeneity of TTNtv dilated cardiomyopathy can be modeled in adult zebrafish.JCI insight · 2024Article
- Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies.Scientific reports · 2024Review
- Control of NADThe EMBO journal · 2024Article
- Transcriptomic analysis reveals novel hub genes associated with astrocyte autophagy in intracerebral hemorrhage.Frontiers in aging neuroscience · 2024Article
- Mitophagy for cardioprotection.Basic research in cardiology · 2023Review
- Myokine Musclin Is Critical for Exercise-Induced Cardiac Conditioning.International journal of molecular sciences · 2023Article
- Transcriptional and post-transcriptional control of autophagy and adipogenesis by YBX1.Cell death & disease · 2023Article
- The Role of MicroRNAs in Dilated Cardiomyopathy: New Insights for an Old Entity.International journal of molecular sciences · 2022Review
- Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications.Acta pharmaceutica Sinica. B · 2022Review
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Impairments in macroautophagy/autophagy, which degrades dysfunctional organelles as well as long-lived and aggregate proteins, are associated with several cardiomyopathies; however, the regulation of cardiac autophagy remains insufficiently understood. In this regard, ULK1 and ULK2 are thought to play primarily redundant roles in autophagy initiation, but whether their function is developmentally determined, potentially having an impact on cardiac integrity and function remains unknown. Here, we demonstrate that perinatal loss of ULK1 or ULK2 in cardiomyocytes (cU1-KO and cU2-KO mice, respectively) enhances basal autophagy without altering autophagy machinery content while preserving cardiac function. This increased basal autophagy is dependent on the remaining ULK protein given that perinatal loss of both ULK1 and ULK2 in cU1/2-DKO mice impaired autophagy causing age-related cardiomyopathy and reduced survival. Conversely, adult loss of cardiac ULK1, but not of ULK2 (i.e., icU1-KO and icU2-KO mice, respectively), led to a rapidly developing cardiomyopathy, heart failure and early death. icU1-KO mice had impaired autophagy with robust deficits in mitochondrial respiration and ATP synthesis. Trehalose ameliorated autophagy impairments in icU1-KO hearts but did not delay cardiac dysfunction suggesting that ULK1 plays other critical, autophagy-independent, functions in the adult heart. Collectively, these results indicate that cardiac ULK1 and ULK2 are functionally redundant in the developing heart, while ULK1 assumes a more unique, prominent role in the adult heart.
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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.