Perturbation of mitochondrial Ca²⁺ homeostasis activates cross-compartmental proteostatic response in Arabidopsis

Abstract Mitochondrial Ca 2+ ( mt Ca 2+ ) homeostasis is essential to mitochondrial functions. However, how mt Ca 2+ homeostasis is achieved and the consequences of impaired mt Ca 2+ homeostasis in plants is poorly understood. Here, we demonstrate a critical role for mitochondrial Ca 2+ uniporter (MCU) in the control of mt Ca 2+ uptake for mt Ca 2+ homeostasis in planta by characterizing MCU mutants and overexpressed plants. Impaired MCU-controlled mt Ca 2+ homeostasis (iMUCH) in gain-of-function and loss-of-function MCU plants causes the misregulation of mitochondrial gene expression that triggers mitonuclear protein imbalance. Transcriptome integrated with proteomics analysis reveal activation of multiple compartmental UPR gene expression and decrease of cytosolic translation with selective repression of ribosome and RNA modification protein synthesis upon iMUCH. Intriguingly, TOR signalling is not involved in cytosolic translational response to iMUCH, but the reduction of eIFα phosphorylation is evident under iMUCH induced mitochondrial stress. Thus, our study unveils the essential functions of MCU proteins for mt Ca 2+ homeostasis, and the involvement of MCU-controlled mt Ca 2+ homeostasis in mitochondrial stress dependent regulation of protein synthesis for cellular proteostasis that is connected to plant growth and stress resistance.