Perspective proposing that hepatic stress—through bile acid–driven dysbiosis and mitochondrial antigen presentation—may expose mitochondrial antigens and elicit autoimmune responses that contribute to Parkinson's disease initiation and progression.

Highlights a testable liver–mitochondria–immune axis that connects metabolism, microbiome, and immune activation and suggests new biomarker and therapeutic avenues (e.g., bile-acid modulation, microbiome or liver-targeted immune interventions), though the idea remains speculative and requires…

Parkinson's disease (PD) is increasingly understood as a systemic disorder with early manifestations outside the central nervous system. Converging clinical, metabolic, and immunological observations highlight overlaps between PD and primary biliary cholangitis (PBC), a prototypic autoimmune cholestatic liver disease. A shared hallmark of both conditions is mitochondrial dysfunction and immune dysregulation, particularly in the context of bile acid (BA) metabolism. In this Current Opinion-style perspective, we integrate recent advances in microbiome biology, BA signaling, and mitochondrial antigen presentation to propose that hepatic stress may contribute to PD pathogenesis by promoting immune exposure to mitochondrial antigens, a proautoimmune cytokine environment, and the generation of mitochondrial‑reactive cytotoxic T cell responses. We discuss how alterations in BA and the promotion of dysbiosis - documented in both PBC and PD - can induce ductular reaction, immunogenic apoptosis, and MitAP, thereby providing a mechanistic bridge between liver inflammation and adaptive immunity. Despite divergent clinical presentations, PBC and PD may share critical upstream pathways linking hepatic metabolism, mitochondrial antigenicity, and immune tolerance. We argue that further investigation of a liver-mitochondria-immune axis may yield new insights into PD initiation and progression.