The proline cycle as an eukaryotic redox valve

Abstract

The amino acid proline has been known for many years to be a component of proteins as well as an osmolyte. Many recent studies have demonstrated that proline has other roles such as regulating redox balance and energy status. In animals and plants, the well-described proline cycle is concomitantly responsible for the preferential accumulation of proline and shuttling of redox equivalents from the cytosol to mitochondria. The impact of the proline cycle goes beyond regulating proline levels. In this review, we focus on recent evidence of how the proline cycle regulates redox status in relation to other redox shuttles. We discuss how the interconversion of proline to glutamate shuttles reducing power between cellular compartments. Spatial aspects of the proline cycle in the entire plant are considered in terms of proline transport between organs with different metabolic regimes (photosynthesis versus respiration). Furthermore, we highlight the importance of this shuttle in the regulation of energy and redox power in plants, through a particularly intricate coordination notably between mitochondria and cytosol.

Intriguing Role of Proline in Redox Potential Conferring High Temperature Stress Tolerance

“…Interestingly, in A. thaliana , stimulation or inhibition by chloride ions and feedback regulation by proline depends on whether NADPH or NADH acts as co-substrate ( Giberti et al, 2014 ). This infers that activities of P5CS and P5CR lower the concentrations of NADPH/NADP + ratio in the cytosol ( Liang et al, 2013 ; Zheng et al, 2021 , Lehr et al, 2022 ). While proline suppressed the activity of only NADH-dependent enzymes, salt stimulated the NADPH-dependent reaction ( Giberti et al, 2014 ).…”

“…The regulatory roles of proline and proline cycle in heat stress have been emphasized by Iqbal et al (2019) , Zheng et al (2021) , and Lehr et al (2022) . Through diverse molecular methods, key genes involved in proline biosynthesis and degradation (proline cycle; Figure 1 ) have been identified in plants ( Deuschle et al, 2001 ).…”

“…Such proline/P5C toxicity could be because of an overflow of electrons in the mitochondrial electron transport chain (mETC). The increase in ROS was caused by inhibiting P5CDH or yeast mutants lacking this enzyme, demonstrating that P5C functions as a stress response regulator and that its levels must be strictly maintained ( Deuschle et al, 2001 ; Zheng et al, 2021 ). Thus, the redox state, as well as chloride and proline concentrations in the cytosol, govern all enzymatic activities of the proline cycle in a complicated way.…”

TKTL1 Knockdown Impairs Hypoxia-Induced Glucose-6-phosphate Dehydrogenase and Glyceraldehyde-3-phosphate Dehydrogenase Overexpression

“…Taking into account that TKTL1 knockdown results in a decrease in G6PD activity and that proline synthesis requires NADPH, these results could be explained by a decreased NADPH pool triggered by G6PD activity deficiency. In fact, there is increasing evidence that proline synthesis plays a key role in the regulation of cellular redox homeostasis and that it is synthesized beyond the cell proliferative need as part of a “redox valve” mechanism [ 62 ].…”

The Emerging Role of Proline in the Establishment and Functioning of Legume-Rhizobium Symbiosis

“…An increasing body of evidence shows that the balance between such reactive species and antioxidants systems regulates the onset of symbiosis and nodule development through controlling the redox status in legume nodules ( Damiani et al, 2016 ; Matamoros and Becana, 2020 ). Although the possibility that proline may act as ROS scavenger has not been confirmed ( Forlani et al, 2019 ), several recent studies showed that the interconversion of glutamate and proline may regulate the redox balance and the energy status of the cell in connection with other redox shuttles ( Zheng et al, 2021 ). Accordingly, most enzymes in proline metabolism influence, and are regulated by, the intracellular NAD(P) + /NAD(P)H ratio ( Giberti et al, 2014 ; Sabbioni et al, 2021 ).…”