Mitophagy in plants: Emerging regulators of mitochondrial targeting for selective autophagy.

The degradation and turnover of mitochondria is fundamental to Eukaryotes and is a key homeostatic mechanism for maintaining functional mitochondrial populations. Autophagy is an important pathway by which mitochondria are degraded, involving their sequestration into membrane-bound autophagosomes and targeting to lytic endosomal compartments (the lysosome in animals, the vacuole in plants and yeast). Selective targeting of mitochondria for autophagy, also known as mitophagy, distinguishes mitochondria from other cell components for degradation and is necessary for the regulation of mitochondria-specific cell processes. In mammals and yeast, mitophagy has been well characterised and is regulated by numerous pathways with diverse and important functions in the regulation of cell homeostasis, metabolism and responses to specific stresses. In contrast, we are only just beginning to understand the importance and functions of mitophagy in plants, chiefly as the proteins that target mitochondria for autophagy in plants are only recently emerging. Here, we discuss the current progress of our understanding of mitophagy in plants, the importance of mitophagy for plant life and the regulatory autophagy proteins involved in mitochondrial degradation. In particular, we will discuss the recent emergence of mitophagy receptor proteins that selectively target mitochondria for autophagy, and discuss the missing links in our knowledge of mitophagy-regulatory proteins in plants compared to animals and yeast.

Novel mechanism of positive versus negative regulation by thyroid hormone receptor ß1 (TRß1) identified by genome-wide profiling of binding sites in mouse liver.

Triiodothyronine (T3) regulates key metabolic processes in the liver through the thyroid hormone receptor, TRß1. However, the number of known target genes directly regulated by TRß1 is limited, and the mechanisms by which positive and especially negative transcriptional regulation occur are not well understood. To characterize the TRß1 cistrome in vivo, we expressed a biotinylated TRß1 in hypo- and hyperthyroid mouse livers, used ChIP-seq to identify genomic TRß1 targets, and correlated these data with gene expression changes. As with other nuclear receptors, the majority of TRß1 binding sites were not in proximal promoters but in the gene body of known genes. Remarkably, T3 can dictate changes in TRß1 binding, with strong correlation to T3-induced gene expression changes, suggesting that differential TRß1 binding regulates transcriptional outcome. Additionally, DR-4 and DR-0 motifs were significantly enriched at binding sites where T3 induced an increase or decrease in TRß1 binding, respectively, leading to either positive or negative regulation by T3. Taken together, the results of this study provide new insights into the mechanisms of transcriptional regulation by TRß1 in vivo.

Postnatal regulation of B-1a cell development and survival by the CIC-PER2-BHLHE41 axis.

B-1 cell development mainly occurs via fetal and neonatal hematopoiesis and is suppressed in adult bone marrow hematopoiesis. However, little is known about the factors inhibiting B-1 cell development at the adult stage. We report that capicua (CIC) suppresses postnatal B-1a cell development and survival. CIC levels are high in B-1a cells and gradually increase in transitional B-1a (TrB-1a) cells with age. B-cell-specific Cic-null mice exhibit expansion of the B-1a cell population and a gradual increase in TrB-1a cell frequency with age but attenuated B-2 cell development. CIC deficiency enhances B cell receptor (BCR) signaling in transitional B cells and B-1a cell viability. Mechanistically, CIC-deficiency-mediated Per2 derepression upregulates Bhlhe41 levels by inhibiting CRY-mediated transcriptional repression for Bhlhe41, consequently promoting B-1a cell formation in Cic-null mice. Taken together, CIC is a key transcription factor that limits the B-1a cell population at the adult stage and balances B-1 versus B-2 cell formation.

TRB1 negatively regulates gluconeogenesis by suppressing the transcriptional activity of FOXO1.

Tribbles related homolog 1 is the mammalian ortholog of Tribbles, which controls cell division and migration during development in Drosophila. TRB1 is a pseudokinase and functions as a scaffold protein. Recent findings suggest that TRB1 plays important roles in hepatic lipid metabolism and participates in insulin resistance. However, the underlying mechanisms have not yet been elucidated. Here, we demonstrate that TRB1 suppresses FOXO1 transcriptional activity to downregulate the expression of G6Pase and PEPCK, which encode gluconeogenic rate-limiting enzymes. TRB1 knockdown enhances FOXO1 binding to the gluconeogenic gene promoters. It also increases FOXO1 acetylation and recruits CBP to the binding sequence of FOXO1. These results suggest that TRB1 suppresses the expression of G6Pase and PEPCK by attenuating FOXO1 transcriptional activity and negatively regulates gluconeogenesis.