透明细胞肾细胞癌（ccRCC）是最常见的肾癌类型，具有高度异质性和复杂性。最近的研究发现线粒体缺陷和自噬是 ccRCC 发展的关键因素。本研究旨在深入探讨ccRCC内线粒体自噬活性的变化及其对肿瘤微环境的影响，揭示其在肿瘤细胞代谢、发育和生存策略中的作用。利用单细胞测序和空间转录组学对ccRCC肿瘤组织进行全面分析，揭示线粒体自噬在 ccRCC 中的作用。通过基因组评分确定肾透明细胞的线粒体自噬发生了改变。使用 NMF 分析和生存分析方法鉴定了关键线粒体自噬细胞群和关键预后基因。体外实验也证明了UBB在ccRCC中的作用。与正常肾组织相比，ccRCC肿瘤组织内的各种细胞类型表现出线粒体自噬水平显着升高，尤其是肾透明细胞。确定了与线粒体自噬水平增加相关的关键基因，如 UBC、UBA52、TOMM7、UBB、MAP1LC3B 和 CSNK2B，它们的高表达与患者不良预后密切相关。特别是，涉及UBB基因的泛素化过程被发现对于线粒体自噬及其质量控制至关重要。本研究强调了线粒体自噬及其调控因子在ccRCC发展中的核心作用，揭示了UBB基因及其相关泛素化的重要性疾病进展过程。版权所有 © 2024 Jiang、Ren、Yang、Chen、Zhang、Zhou、Huang、Jiang、Gu、Tang、Yang、Chi 和 Qing。

Clear Cell Renal Cell Carcinoma (ccRCC) is the most common type of kidney cancer, characterized by high heterogeneity and complexity. Recent studies have identified mitochondrial defects and autophagy as key players in the development of ccRCC. This study aims to delve into the changes in mitophagic activity within ccRCC and its impact on the tumor microenvironment, revealing its role in tumor cell metabolism, development, and survival strategies.Comprehensive analysis of ccRCC tumor tissues using single cell sequencing and spatial transcriptomics to reveal the role of mitophagy in ccRCC. Mitophagy was determined to be altered among renal clear cells by gene set scoring. Key mitophagy cell populations and key prognostic genes were identified using NMF analysis and survival analysis approaches. The role of UBB in ccRCC was also demonstrated by in vitro experiments.Compared to normal kidney tissue, various cell types within ccRCC tumor tissues exhibited significantly increased levels of mitophagy, especially renal clear cells. Key genes associated with increased mitophagy levels, such as UBC, UBA52, TOMM7, UBB, MAP1LC3B, and CSNK2B, were identified, with their high expression closely linked to poor patient prognosis. Particularly, the ubiquitination process involving the UBB gene was found to be crucial for mitophagy and its quality control.This study highlights the central role of mitophagy and its regulatory factors in the development of ccRCC, revealing the significance of the UBB gene and its associated ubiquitination process in disease progression.Copyright © 2024 Jiang, Ren, Yang, Chen, Zhang, Zhou, Huang, Jiang, Gu, Tang, Yang, Chi and Qin.