2025/12/13 by Annie Sahota, Binoy Paulose Nadappuram, Siân C. Allerton +9 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Adipose Tissue and Metabolism #Mitochondrial Function and Pathology #Single-cell and spatial transcriptomics
paper · doi:10.64898/2025.12.10.693488
openalex created_date 2025/12/13 · openalex publication_date 2025/12/13 · openalex updated_date 2026/07/14
Abstract Neurons are highly polarised cells that depend on mitochondria for energy and signalling homeostasis. Importantly, energy and signalling requirements vary considerably across individual neurons both spatially and temporally. Therefore, to fully understand neuronal mitochondria, methods are needed to analyse mitochondria in live cells over time. The nanotweezer, a minimally invasive single-cell sampling technique, enables precise extraction a individual mitochondria from defined subcellular locations. Here, we combine single-mitochondrial extraction from live neurons with mitochondrial gene expression tracking and mtDNA profiling. By tracking mitochondrial gene expression in the same neurons over time, we reveal a downregulation of mitochondrial genes MT-ND1 and MT-ATP6 following exposure to α-synuclein aggregates, independent of the proximity of the aggregates to the sampled mitochondria. Our approach provides precise, dynamic measurements of mitochondrial composition and gene expression in vivo at single-organelle resolution, enabling mechanistic studies of neuronal mitochondrial heterogeneity and its perturbation in models of neurodegeneration.