Physiological mitophagy dynamics across neural space and time
by Assoc. Prof. Thomas McWilliams, University of Helsinki.
Abstract
This Mitophagy sustains lifelong neural integrity by eliminating dysfunctional mitochondria, thereby alleviating metabolic stress. While mitophagy declines with age in short-lived model organisms, its physiological regulation in the aging mammalian brain has remained poorly defined. Using high-resolution spatiocellular mapping of genetically encoded optical reporter mice, we reveal striking cell type-specific differences in basal mitophagy in vivo, challenging the notion of a uniform homeostatic process in the mammalian brain. We further reveal previously underexplored cellular subsets where mitophagy is either sustained or decreased in aging, providing mechanistic insights into neural resilience and selective vulnerability in vivo. Critically, our longitudinal data pinpoint midlife as a critical inflection point hallmarked by emergent lysosomal dysfunction that may prime specific neuronal populations for later decline. Integrating these findings with emerging human data and unconventional model systems, I will discuss how the spatiotemporal modulation of organelle homeostasis in neural networks shapes age-related neurological decline. Our work recasts physiological mitophagy as a dynamic cell and circuit-specific process in vivo, with direct implications for preserving brain health during aging.
Thomas McWilliams is Associated Professor of Mitochondrial Medicine at the University of Helsinki. McWilliams received last year the prestigious Anders Jahre prize for young scientists. The Anders Jahre medical prizes reward excellent research in basal and clinical medicins and is among the largest medical prizes in the Nordic countries.