Proteomics

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Age induced interactome remodeling in muscle mitochondria


ABSTRACT: A novel quantitative crosslinking mass spectrometry technique (qXL-MS) was applied to elucidate interactome changes in aged murine skeletal muscle mitochondria that contribute to age-related mitochondrial functional decline. Reported here are results from initial investigations of murine muscle mitochondrial interactomes that enable identification of statistically significant changes associated with aging. Newly developed isobaric quantitative protein interaction reporter (iqPIR) technologies15 enabled reproducible detection of age-related mitochondrial interactome changes. Muscle mitochondria from young and old mice were isolated, cross-linked with iqPIR molecules, young and old mitochondrial samples were paired, process and analyzed to quantify age-related mitochondrial interactome changes. In parallel, mitochondria were also subjected to additional measurements of mitochondrial protein yield, functional measurements including oxygen consumption rates on Complex I and Complex II substrates, and citrate synthase activity.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skeletal Muscle

DISEASE(S): Disease Free

SUBMITTER: Anna Bakhtina  

LAB HEAD: James E. Bruce

PROVIDER: PXD031643 | Pride | 2024-05-23

REPOSITORIES: Pride

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Publications

Skeletal muscle mitochondrial interactome remodeling is linked to functional decline in aged female mice.

Bakhtina Anna A AA   Pharaoh Gavin A GA   Campbell Matthew D MD   Keller Andrew A   Stuppard Rudolph S RS   Marcinek David J DJ   Bruce James E JE  

Nature aging 20230302 3


Genomic, transcriptomic and proteomic approaches have been used to gain insight into molecular underpinnings of aging in laboratory animals and in humans. However, protein function in biological systems is under complex regulation and includes factors besides abundance levels, such as modifications, localization, conformation and protein-protein interactions. By making use of quantitative chemical cross-linking technologies, we show that changes in the muscle mitochondrial interactome contribute  ...[more]

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