Usage Information
Abstract
Mitochondrial quality control is mediated by the PTEN-induced kinase 1 (PINK1), a cytoprotective protein that is dysregulated in inflammatory lung injury and neurodegenerative diseases. Here, we show that a ubiquitin E3 ligase receptor component, FBXO7, targets PINK1 for its cellular disposal. FBXO7, by mediating PINK1 ubiquitylation and degradation, was sufficient to induce mitochondrial injury and inflammation in experimental pneumonia. A computational simulation–based screen led to the identification of a small molecule, BC1464, which abrogated FBXO7 and PINK1 association, leading to increased cellular PINK1 concentrations and activities, and limiting mitochondrial damage. BC1464 exerted antiinflammatory activity in human tissue explants and murine lung inflammation models. Furthermore, BC1464 conferred neuroprotection in primary cortical neurons, human neuroblastoma cells, and patient-derived cells in several culture models of Parkinson’s disease. The data highlight a unique opportunity to use small molecule antagonists that disrupt PINK1 interaction with the ubiquitin apparatus to enhance mitochondrial quality, limit inflammatory injury, and maintain neuronal viability.
Authors
Yuan Liu, Travis B. Lear, Manish Verma, Kent Z.Q. Wang, P. Anthony Otero, Alison C. McKelvey, Sarah R. Dunn, Erin Steer, Nicholas W. Bateman, Christine Wu, Yu Jiang, Nathaniel M. Weathington, Mauricio Rojas, Charleen T. Chu, Bill B. Chen, Rama K. Mallampalli
Usage data is cumulative from August 2025 through August 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 2,156 | 194 |
| 240 | 53 | |
| Figure | 1,190 | 22 |
| Supplemental data | 136 | 5 |
| Citation downloads | 332 | 0 |
| Totals | 4,054 | 274 |
| Total Views | 4,328 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
