In Rhodotorula mucilaginosa, active oxidative metabolism increases carotenoids to inactivate excess reactive oxygen species

Front Fungal Biol. 2024 Sep 6:5:1378590. doi: 10.3389/ffunb.2024.1378590. eCollection 2024.

Abstract

Carotenoids produced by bacteria, yeasts, algae and plants inactivate Free Radicals (FR). However, FR may inactivate carotenoids and even turn them into free radicals. Oxidative metabolism is a source of the highly motile Reactive Oxygen Species (ROS). To evaluate carotenoid interactions with ROS, the yeast Rhodotorula mucilaginosa was grown in dextrose (YPD), a fermentative substrate where low rates of oxygen consumption and low carotenoid expression were observed, or in lactate (YPLac), a mitochondrial oxidative-phosphorylation (OxPhos) substrate, which supports high respiratory activity and carotenoid production. ROS were high in YPLac-grown cells and these were unmasked by the carotenoid production-inhibitor diphenylamine (DPA). In contrast, in YPD-grown cells ROS were almost absent. It is proposed that YPLac cells are under oxidative stress. In addition, YPLac-grown cells were more sensitive than YPD-grown cells to menadione (MD), a FR-releasing agent. To test whether carotenoids from cells grown in YPLac had been modified by ROS, carotenoids from each, YPD- and YPLac-grown cells were isolated and added back to cells, evaluating protection from MD. Remarkably, carotenoids extracted from cells grown in YPLac medium inhibited growth, while in contrast extracts from YPD-grown cells were innocuous or mildly protective. Results suggest that carotenoid-synthesis in YPLac-cells is a response to OxPhos-produced ROS. However, upon reacting with FR, carotenoids themselves may be inactivated or even become prooxidant themselves.

Keywords: ROS; Rhodotorula mucilaginosa; aerobic metabolism; carbon source; carotenoids; diphenylamine (DPA).

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was partially funded by research grants to SU-C: CONAHCYT CF2023-I-199 and from UNAM/DGAPA/PAPIIT IN211224 and to MG-A: UNAM/DGAPA/PAPIIT IN217624. OM-R has a Postdoctoral fellowship from CONAHCYT CVU 639365. EM-M is a MsC CONAHCYT fellow CVU 1184243 enrolled in the Ciencias Bioquímicas Program at UNAM. PC-T is a PhD CONAHCYT fellow CVU 708685 enrolled in the Ciencias Bioquímicas Program at UNAM. CR-G is a PhD CONAHCYT fellow, CVU 966402 enrolled in the Ciencias Bioquímicas Program at UNAM.