Correlative MIMS-EM imaging reveals metabolic turnover from organelle to organismal scales in C. elegans during dietary restriction

Researchers have discovered that metabolic turnover occurs at various scales within Caenorhabditis elegans, from individual organelles to entire organisms, during dietary restriction (DR). Traditionally, metabolic studies have overlooked spatial organization and heterogeneity within smaller measurements. To address this limitation, a team adapted multi-isotope mass spectrometry coupled with scanning electron microscopy (MIMS-EM) for C. elegans.

This technique allows for in situ mapping of nutrient fates at nanometer-scale resolution, preserving ultrastructural context.

Using pulse-chase labeling of dietary carbon and nitrogen, the researchers applied MIMS-EM to early DR stages to understand the metabolic program induced in these organisms. While DR is known to enhance overall healthspan by promoting broadscale turnover, proteomic studies have provided more nuanced insights. Through MIMS-EM imaging across intact animals, the team found that DR induces non-uniform effects between tissues and carbon/nitrogen resources.

Specifically, carbon turnover was accelerated in the muscle and hypodermis, but not in the intestine.

At the organelle scale, MIMS-EM revealed heterogeneity within mitochondrial networks that was independent of diet and remained stable over time. Spatial analysis of isotope signatures within intestinal mitochondrial networks further supported the idea of greater similarity between neighboring mitochondria compared to distal ones, suggesting models of local mitochondrial mixing.

By conducting this comprehensive analysis, the researchers demonstrated that DR triggers compartment- and resource-specific remodeling strategies within an intact C. elegans organism. Furthermore, they established the MIMS-EM platform as a valuable tool for multi-scale, integrative models of nutrient handling in this model organism.