In vivo analyses reveal rapid and permissive lipid transport between the ER and mitochondria
Abstract
Interorganelle lipid transport is essential for mitochondrial membrane biogenesis and function, yet its kinetics and substrate selectivity remain poorly understood in vivo . Here, we developed two complementary approaches to quantify lipid trafficking from the endoplasmic reticulum (ER) to mitochondria in yeast. Metabolic labeling combined with organelle fractionation revealed that newly synthesized phospholipids rapidly accumulate in mitochondria, with 20-35% of newly synthesized molecules detected in mitochondrial fractions within minutes of synthesis. To directly quantify lipid flux, we established a synthetic transport assay based on the production of heterologous galactolipids absent from yeast. This approach revealed an ER-to-mitochondria transport flux of approximately 2.6 x 10 5 lipid molecules per cell per minute. Remarkably, galactolipids were transported with high efficiency despite their absence from fungal membranes, indicating limited substrate selectivity of ER-mitochondria lipid transport pathways. Together, these complementary assays provide quantitative tools to investigate intracellular lipid transport and reveal the rapid and permissive nature of lipid exchange between the ER and mitochondria. Summary Using complementary metabolic labeling and synthetic lipid reporter assays, we quantitatively measured ER-mitochondria lipid transport in yeast. Our results reveal rapid lipid exchange, high transport fluxes and limited substrate selectivity, indicating that mitochondrial lipid trafficking efficiently accommodates structurally diverse membrane lipids.
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BibTeX
@misc{montmayeul2026vivo,
title = {{In vivo analyses reveal rapid and permissive lipid transport between the ER and mitochondria}},
author = {Paul Montmayeul and Samantha Voguin and Catherine Albrieux and Hanna Kulyk and Lindsay Peyriga and Floriant Bellvert and Lucas Place and Marion Schilling and Juliette Jouhet and Alexandre Toulmay and William Prinz and Morgane Michaud},
howpublished = {HAL},
year = {2026},
month = jun,
doi = {10.64898/2026.06.18.733118},
url = {https://hal.science/hal-05851219v1},
note = {CC BY-NC 4.0},
}
RIS
TY - UNPB
TI - In vivo analyses reveal rapid and permissive lipid transport between the ER and mitochondria
AU - Paul Montmayeul
AU - Samantha Voguin
AU - Catherine Albrieux
AU - Hanna Kulyk
AU - Lindsay Peyriga
AU - Floriant Bellvert
AU - Lucas Place
AU - Marion Schilling
AU - Juliette Jouhet
AU - Alexandre Toulmay
AU - William Prinz
AU - Morgane Michaud
PY - 2026
DA - 2026/06/19
PB - HAL
DO - 10.64898/2026.06.18.733118
UR - https://hal.science/hal-05851219v1
AB - Interorganelle lipid transport is essential for mitochondrial membrane biogenesis and function, yet its kinetics and substrate selectivity remain poorly understood in vivo . Here, we developed two complementary approaches to quantify lipid trafficking from the endoplasmic reticulum (ER) to mitochondria in yeast. Metabolic labeling combined with organelle fractionation revealed that newly synthesized phospholipids rapidly accumulate in mitochondria, with 20-35% of newly synthesized molecules detected in mitochondrial fractions within minutes of synthesis. To directly quantify lipid flux, we established a synthetic transport assay based on the production of heterologous galactolipids absent from yeast. This approach revealed an ER-to-mitochondria transport flux of approximately 2.6 x 10 5 lipid molecules per cell per minute. Remarkably, galactolipids were transported with high efficiency despite their absence from fungal membranes, indicating limited substrate selectivity of ER-mitochondria lipid transport pathways. Together, these complementary assays provide quantitative tools to investigate intracellular lipid transport and reveal the rapid and permissive nature of lipid exchange between the ER and mitochondria. Summary Using complementary metabolic labeling and synthetic lipid reporter assays, we quantitatively measured ER-mitochondria lipid transport in yeast. Our results reveal rapid lipid exchange, high transport fluxes and limited substrate selectivity, indicating that mitochondrial lipid trafficking efficiently accommodates structurally diverse membrane lipids.
ER -