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Tissue-specific in vivo mitochondrial matrix proteome profiling in mouse

ABSTRACT: Targeting proximity labeling enzymes to specific cellular locations is a viable strategy for profiling subcellular proteomes with minimal perturbance to normal physiology. Here, we generate transgenic mice expressing a mitochondrial matrix-targeted ascorbate peroxidase (MTS-APEX2) to enable analysis of tissue-specific matrix proteomes. Desthiobiotin-phenol labeling of the mitochondrial proteome revealed 263 mitochondrial-localized proteins in mouse muscle tissues. Comparison with the MTS-APEX2-labeled proteome in HEK293T cells revealed enrichment in mitochondrial proteins related to energy production in the muscle tissues of transgenic mice. We found Reticulon 4 Interacting Protein 1(RTN4IP1) or Optic Atrophhy-10 (OPA10) was highly enriched in cardiac and soleus muscle and contained a strong mitochondrial matrix-targeting sequence. Structural analysis shows RTN4IP1 is an NADPH oxidoreductase with protein structure resembling quinone oxidoreductase (QOR) in bacterial species. Enzymatic activity assays, interactome analysis, and metabolite profiling confirmed that RTN4IP1 functions in coenzyme Q biosynthesis in the mitochondria. Due to reduced CoQ9 levels, Rtn4ip1-knockout C2C12 cells were vulnerable to oxidative stress and had decreased oxygen consumption rates and ATP production.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Heart, Soleus, Hek-293 Cell, Tibialis Anterior

SUBMITTER: Jong-Seo Kim

LAB HEAD: Jong-Seo Kim

PROVIDER: PXD026793 | Pride | 2023-08-31

REPOSITORIES: Pride

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