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Long-lived mitochondrial cristae proteins in mouse heart and brain

ABSTRACT: Long-lived proteins (LLPs) have recently emerged as vital components of intracellular structures whose function is coupled to long-term stability. Mitochondria are multifaceted organelles and their function hinges on the efficient proteome renewal and replacement. Here, using metabolic stable isotope labelling of mice combined with mass spectrometry (MS) based proteomic analysis we demonstrate remarkable longevity for a subset of the mitochondrial proteome. We discovered that mitochondrial LLPs (mt-LLPs) can persist for months in tissues harboring long-lived cells, such as brain and heart. Our analysis revealed an enrichment of mt-LLPs within the inner mitochondrial membrane, specifically in the cristae sub-compartment, and demonstrate that the mitochondrial proteome is not turned over in bulk. Pioneering crosslinking experiments revealed that mt-LLPs are spatially restricted and co-preserved within protein OXPHOS complexes with limited subunit exchange throughout their lifetime. This study provides an explanation for the exceptional mitochondrial protein lifetimes and supports the concept that LLPs provide key structural stability to multiple large and dynamic intracellular structures.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Jeffrey N. Savas, PhD

PROVIDER: MSV000087712 | MassIVE | Mon Jun 28 15:29:00 BST 2021

SECONDARY ACCESSION(S): PXD027060

REPOSITORIES: MassIVE

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