Sakellakis Minas, Flores Laura Jacqueline
Department of Genitourinary Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
Curr Urol. 2022 Dec;16(4):207-212. doi: 10.1097/CU9.0000000000000120. Epub 2022 Aug 31.
Mitochondria are more than just the cellular powerhouse. They also play key roles in vital functions such as apoptosis, metabolism regulation, and other intracellular interactions. The mitochondrial DNA (mtDNA) encodes for 12 subunits of the oxidative phosphorylation (OXPHOS) system. Depletion of mtDNA in androgen-dependent prostate cancer (PCa) cell lines renders them androgen-independent and more aggressive. Paradoxically, pharmaceutical inhibition of OXPHOS is lethal for subsets of PCa cells, whereas others become dependent on androgen receptor (AR) signaling for survival. Given that the AR-mitochondria interaction is critical for early PCa, it is crucial to understand the details of this interaction. Technical hurdles have made mitochondria traditionally difficult to study, with many techniques used for isolation masking the properties of given individual mitochondria. Although the isolation of mitochondria enables us to study OXPHOS, we miss the context in which mitochondria interact with the rest of the cell. Both AR signaling and mtDNA affect apoptosis, metabolism regulation, cellular calcium storage and homeostasis, intracellular calcium signaling, and redox homeostasis. In this review, we will attempt to understand how the crosstalk between AR-mtDNA-OXPHOS is responsible for "life or death" decisions inside the cells. Our aim is to point toward potential vulnerabilities that can lead to the discovery of novel therapeutic targets.
线粒体不仅仅是细胞的动力源。它们在细胞凋亡、代谢调节和其他细胞内相互作用等重要功能中也发挥着关键作用。线粒体DNA（mtDNA）编码氧化磷酸化（OXPHOS）系统的12个亚基。雄激素依赖性前列腺癌细胞系中线粒体DNA的耗竭使其变得不依赖雄激素且更具侵袭性。矛盾的是，OXPHOS的药物抑制对部分前列腺癌细胞是致命的，而其他细胞则变得依赖雄激素受体（AR）信号来维持生存。鉴于AR-线粒体相互作用对早期前列腺癌至关重要，了解这种相互作用的细节至关重要。技术障碍使得线粒体传统上难以研究，许多用于分离的技术掩盖了单个线粒体的特性。虽然线粒体的分离使我们能够研究OXPHOS，但我们忽略了线粒体与细胞其他部分相互作用的背景。AR信号和mtDNA都影响细胞凋亡、代谢调节、细胞钙储存和稳态、细胞内钙信号以及氧化还原稳态。在这篇综述中，我们将试图了解AR-mtDNA-OXPHOS之间的相互作用是如何决定细胞内“生死”抉择的。我们的目的是指出潜在的脆弱点，从而发现新的治疗靶点。
