Endoplasmic reticulum–mitochondria contact sites in benign prostatic hyperplasia: evidence integration and mechanistic hypotheses

Abstract

Benign prostatic hyperplasia (BPH) is a common chronic and progressive disease in ageing men. Its pathobiology involves androgen-signaling remodeling, chronic inflammation, oxidative stress, metabolic disturbance, and dysregulated cell fate control; however, the organelle-level communication that connects these processes remains insufficiently defined. Endoplasmic reticulum (ER)–mitochondria contact sites, commonly referred to as mitochondria-associated membranes (MAMs), are dynamic membrane contact platforms that coordinate ER stress with mitochondrial homeostasis. Through the regulation of Ca²+ transfer, lipid metabolism, mitochondrial dynamics, autophagy, inflammatory signaling, and cell death, MAMs may provide a structural and functional interface linking several pathological features of BPH. In this review, we integrate evidence from BPH studies, including GRP78 upregulation, mitochondrial reactive oxygen species (ROS) accumulation, NLRP3 inflammasome activation, DRP1-associated abnormalities in mitochondrial dynamics, and resistance to apoptosis. On this basis, we discuss the mechanistic hypothesis that MAM remodeling may contribute to the chronic progression of BPH. Current evidence does not support defining MAMs as direct pathogenic drivers of BPH. Rather, positioning MAMs as an organelle-communication framework that links ER stress, mitochondrial injury, and tissue hyperplasia may help explain the pathological heterogeneity of BPH and identify candidate targets for future investigation.