Iron Deficiency and Recovery in Yeast: A Quantitative Proteomics Approach

Iron
is an essential element for life, as it is critical for oxygen
transport, cellular respiration, DNA synthesis, and metabolism. Disruptions
in iron metabolism have been associated with several complex diseases
like diabetes, cancer, infection susceptibility, neurodegeneration,
and others; however, the molecular mechanisms linking iron metabolism
with these diseases are not fully understood. A commonly used model
to study iron deficiency (ID) is yeast, Saccharomyces cerevisiae. Here, we used quantitative (phospho)­proteomics to explore the early
(4 and 6 h) and late (12 h) response to ID. We showed that metabolic
pathways like the Krebs cycle, amino acid, and ergosterol biosynthesis
were affected by ID. In addition, during the late response, several
proteins related to the ubiquitin-proteasome system and autophagy
were upregulated. We also explored the proteomic changes during a
recovery period after 12 h of ID. Several proteins recovered their
steady-state levels, but some others, such as cytochromes, did not
recover during the time tested. Additionally, we showed that autophagy
is active during ID, and some of the degraded proteins during ID can
be rescued using KO strains for several key autophagy genes. Our results
highlight the complex proteome changes occurring during ID and recovery.
This study constitutes a valuable data set for researchers interested
in iron biology, offering a temporal proteomic data set for ID, as
well as a compendium the proteomic changes associated with episodes
of iron recovery.