Interplay between Mitochondrial Dysfunction, Lipid Dysregulation and Lipid Droplet dynamics in Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a multifactorial neurodegenerative disease associated with dopaminergic neuronal loss and is characterized by both motor and non-motor symptoms. At the cellular level, these neurons are pushed to degeneration due to the accumulation of Lewy bodies (LBs) which are proteinaceous inclusions enriched in α-synuclein (α-syn). Over the past decade, region-specific lipidomic studies have uncovered a spectrum of lipid changes in post-mortem PD brains, suggesting a widespread disruption of cellular lipid homeostasis. The challenge of monitoring brain lipidomes in living patients at early disease stages has driven the search for identifying altered lipid signatures in peripheral blood for understanding the disease progression. Defects in mitochondrial respiration have been implicated in the etiology and pathogenesis of PD (Perier and Vila, 2012). Excess fatty acids get stored in lipid droplets and are detoxified by mitochondrial β-oxidation but dysfunctional mitochondria reduce FA metabolism, causing lipotoxicity and aggravating the PD process (Tong et al., 2024). Several studies have reported altered lipidomic profiles in PD brain and peripheral samples, but studies correlating lipid dysregulation with mitochondrial respiration and lipid droplet dynamics are limited. In this work, we hypothesized that lipid dysregulation leads to lipid droplet accumulation and impaired mitochondrial respiration in peripheral blood samples of PD patients.

Cite: Nataraj P, Krishnan S, Urulangodi M (2026) Interplay between Mitochondrial Dysfunction, Lipid Dysregulation and Lipid Droplet dynamics in Parkinson’s Disease. BEC prep 2026.7 https://doi.org/10.26124/becprep.2026-0007