Using mass spectrometry imaging to visualize age-related subcellular disruption

Abstract

Metabolic homeostasis balances the production and consumption of energetic molecules to maintain active, healthy cells. Cellular stress, which disrupts metabolism and leads to the loss of cellular homeostasis, is important in age-related diseases. We focus here on the role of organelle dysfunction in age-related diseases, including the roles of energy deficiencies, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, changes in metabolic flux in aging (e.g., Ca2+ and nicotinamide adenine dinucleotide), and alterations in the endoplasmic reticulum-mitochondria contact sites that regulate the trafficking of metabolites. Tools for single-cell resolution of metabolite pools and metabolic flux in animal models of aging and age-related diseases are urgently needed. High-resolution mass spectrometry imaging (MSI) provides a revolutionary approach for capturing the metabolic states of individual cells and cellular interactions without the dissociation of tissues. mass spectrometry imaging can be a powerful tool to elucidate the role of stress-induced cellular dysfunction in aging.

3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex

“…Thus, further studies are needed to characterize the association of mitochondria with lipid droplets or interactions with the endoplasmic reticulum (ER) (Ilacqua et al., 2021 ) to determine whether the contact sites change during aging to protect against lipotoxicity. In addition, mass spectrometry imaging may reveal changes in the spatial distribution of these metabolites during aging (Hogan et al., 2023 ). In gastrocnemius tissue, phospholipids decreased (Figure 6 ), as did linoleic acid, which is important for membrane integrity (Cury‐Boaventura et al., 2004 ).…”

Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine

“…These metabolic shifts, when correlated with gene and protein brain atlases, offer insights into brain metabolism’s spatial and temporal dynamics during aging. Additionally, spatial metabolomics techniques have been employed to investigate age-related metabolic changes, revealing spatially distinct metabolic signatures of aging [ 199 ]. Integrating spatial proteomic and metabolomic data has facilitated the identification of molecular interactions and pathways involved in aging [ 200 – 202 ].…”

Global and Spatial Metabolomics of Individual Cells Using a Tapered Pneumatically Assisted nano-DESI Probe

“…12−15 The combined sampling and ionization strategies of individual cells include matrix-assisted laser desorption (MALDI) 16,17 and secondary ion mass spectrometry (SIMS). 18,19 For example, single-cell metabolomics using MALDI has revealed metabolic heterogeneity and states of stimulated dHepaRG hepatocytes, and different metabolic profiles related to inflammatory macrophages have been pinpointed by SIMS. 20,21 Other sampling strategies for single-cell metabolomics are combined with electrospray ionization (ESI) MS. 22,23 For example, electromigration combined with droplet-assisted ESI revealed the importance of isomeric lipids in drug-resistant HCC827 cells.…”

“…Single-cell metabolomics is challenging to achieve. This is partly due to the rapid turnover rate of metabolites but also the high complexity of the metabolome with diverse structures and wide concentration ranges within the picoliter-order cell volume. , Although mass spectrometry (MS) is the main analytical tool used for single-cell metabolomics, it is used in combination with several different sampling and ionization strategies. − The combined sampling and ionization strategies of individual cells include matrix-assisted laser desorption (MALDI) , and secondary ion mass spectrometry (SIMS). , For example, single-cell metabolomics using MALDI has revealed metabolic heterogeneity and states of stimulated dHepaRG hepatocytes, and different metabolic profiles related to inflammatory macrophages have been pinpointed by SIMS. , Other sampling strategies for single-cell metabolomics are combined with electrospray ionization (ESI) MS. , For example, electromigration combined with droplet-assisted ESI revealed the importance of isomeric lipids in drug-resistant HCC827 cells . These and other studies demonstrate the possibility and significance of performing metabolomics on individual cells. − …”