PINK1 link mitochondria-ER contacts controls deposition of intramuscular fat in pigs

Abstract

Intramuscular fat (IMF) is a key determinant of meat quality in pigs, influencing characteristics such as tenderness, flavor, and marbling. The regulation of IMF deposition involves complex metabolic processes, with mitochondrial function playing a central role. PTEN-induced kinase 1 (PINK1), a protein involved in mitophagy and mitochondrial quality control, has recently been implicated in regulating fat deposition, although its role in IMF deposition in pigs remains unclear. This study investigates how PINK1 regulates IMF deposition by modulating mitochondrial-endoplasmic reticulum (ER) interactions. We utilized single-cell RNA sequencing to demonstrate that PINK1 is predominantly expressed in fibro-adipogenic progenitors (FAPs) and adipocytes, and its expression is negatively correlated with IMF content in multiple pig breeds. Knockdown of PINK1 in vivo led to increased intramuscular triglyceride content and enhanced adipogenic differentiation in primary porcine IMF cells. Additionally, PINK1 depletion resulted in impaired mitochondrial respiration, increased mitochondrial biogenesis, and disruption of mitochondria-ER contacts, further suggesting that PINK1 mediated of mitochondrial function and communication between mitochondria and ER is essential for controlling lipid deposition. These findings provide novel insights into the molecular mechanisms governing IMF accumulation and highlight PINK1 as a potential target for manipulating fat deposition in both agricultural and biomedical contexts.