preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints202305.0302.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 4 May 2023 / Approved: 5 May 2023 / Online: 5 May 2023 (04:57:13 CEST)

Dual localization or dual targeting refers to the phenomenon by which identical, or almost identical, proteins are localized to two (or more) separate compartments of the cell. From previous work in the field, we had estimated that a third of the mitochondrial proteome is dual targeted to extra-mitochondrial locations and suggested that this abundant dual targeting presents an evolutionary advantage. Here we set out to study how many additional proteins whose main activity is outside mitochondria are also localized, albeit at low levels, to mitochondria (eclipsed). To do this we employed two complementary approaches utilizing the α-complementation assay in yeast to uncover the extent of such eclipsed distribution: one systematic and unbiased and the other based on Mitochondrial Targeting Signal (MTS) predictions. Using these approaches, we suggest 280 new eclipsed distributed protein candidates. Interestingly, these proteins are enriched for distinctive properties compared to their exclusively mitochondrial-targeted counterparts. We focus on one unexpected eclipsed protein-family of the Triose-phosphate DeHydrogenases (TDH), and prove that indeed their eclipsed distribution in mitochondria is important for mitochondrial activity. Our work provides a paradigm of deliberate eclipsed mitochondrial localization, targeting and function, and should expand our understanding of mitochondrial function in health and disease.

Mitochondria; Eclipsed protein targeting; Yeast model system; TDH1; TDH2; Dual protein tar-geting

Biology and Life Sciences, Biochemistry and Molecular Biology

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