Mitochondrial Alterations in Prostate Cancer: Roles in Pathobiology and Racial Disparities

Abstract

Prostate cancer (PCa) affects millions of men worldwide and is a major cause of cancer-related mortality. Race-associated PCa health disparities are also common and are of both social and clinical concern. Most PCa is diagnosed early due to PSA-based screening, but it fails to discern between indolent and aggressive PCa. Androgen or androgen receptor-targeted therapies are standard care of treatment for locally advanced and metastatic disease, but therapy resistance is common. Mitochondria, the powerhouse of cells, are unique subcellular organelles that have their own genome. A large majority of mitochondrial proteins are, however, nuclear-encoded and imported after cytoplasmic translation. Mitochondrial alterations are common in cancer, including PCa, leading to their altered functions. Aberrant mitochondrial function affects nuclear gene expression in retrograde signaling and promotes tumor-supportive stromal remodeling. In this article, we discuss mitochondrial alterations that have been reported in PCa and review the literature related to their roles in PCa pathobiology, therapy resistance, and racial disparities. We also discuss the translational potential of mitochondrial alterations as prognostic biomarkers and as effective targets for PCa therapy.

Comprehensive overview of how to fade into succinate dehydrogenase dysregulation in cancer cells by naringenin-loaded chitosan nanoparticles

“…This succinate buildup ultimately leads to an epigenetic alteration in carcinomas [ 57 ]. Studies have confirmed the role of succinate in cellular transformation and cancer at both the biochemical and genomic levels [ 66 , 76 ].…”

AGEs and RAGE: metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers

“…Present at the facade of eliciting chemo-resistance, mitochondria regulate molecular interplay at places of cellular stress and facilitate cell survival. Perturbed mitochondrial functions are commonly observed in cancer, often leading to altered nuclear gene expression via retrograde signalling and promotion of tumour endorsing stromal re-modelling [ 51 ]. Evasion of apoptosis and metabolic re-wiring are endorsed by the mitochondrial components invoking chemo-resistance and metastasis of cancers.…”

“…Metabolic interaction between tumor cells and the stromal cells varies in different cancers, giving rise to differences in their aggressive nature. Based on the analysis of glycolytic status of tumours, by evaluating the immunohistochemical expression of GLUT-1 and carbonic anhydrase IX (CAIX) in tissue microarray sections from 740 patients with breast cancer, Choi and colleagues [50] classified the molecular subtypes of breast cancer into the following metabolic strata: Warburg type: tumor-glycolysis type, stroma-nonglycolysis type. (1) Reverse Warburg type: tumor-nonglycolysis type, stroma-glycolysis type.…”

The Regulation Impact of Naringenin-loaded Chitosan Nanoparticles on Succinate Dehydrogenase Activity in Cancer Cells

“…Multiple subcellular compartments, particularly mitochondria, experience global lysine hyper-succinylation as a result of succinate buildup brought on by SDH depletion leading to an epigenetic change in carcinomas [32]. Studies have validated the role of succinate in cellular transformation and cancer at both the biochemical and genomic levels [33,34].…”