1. Organelle crosstalk in the kidney
Tsuyoshi Inoue, Hiroshi Maekawa, Reiko Inagi 
Kidney International 
DOI: /j.kint
Copyright © 2019 International Society of Nephrology Terms and Conditions

2. Figure 1
Brief summary of organelle interactions. Various assemblies of organelle interactions have been shown, highlighting the pathophysiological effect of organelle crosstalk. For example, mitofusin 2 (Mfn2) tethers the endoplasmic reticulum (ER) and mitochondria together for mitochondrial fusion at ER–mitochondria membrane contact sites (MCSs). Stromal interaction molecule 1 (STIM1), localized in the ER, senses a decrease in Ca2+ concentration in the ER, aggregates at the ER–plasma membrane MCS, forms a STIM1-Orai complex, activates Orai, and mediates the inflow of extracellular Ca2+. Ca2+ released from the ER via the inositol trisphosphate receptor (IP3R) is taken up by mitochondria through the voltage-dependent anion channel (VDAC). Ceramide transfer from the ER to the Golgi apparatus is mediated by ceramide transfer protein (CERT). Mitochondrial dysfunction induced by abnormal cilia in tubular epithelial cells aggravates autosomal-dominant polycystic kidney disease, indicating the pathophysiology of mitochondria–cilia interaction in cyst formation. Orai1, ORAI calcium release-activated calcium modulator 1; PGC-1α, peroxisome proliferator-activated receptor γ coactivation-1α; SERCA, sarcoplasmic/endoplasmic reticulum Ca2+-adenosine triphosphatase.
Kidney International DOI: ( /j.kint )
Copyright © 2019 International Society of Nephrology Terms and Conditions

3. Figure 2
Overview of the unfolded protein response (UPR) pathway in the endoplasmic reticulum (ER). ER proteostasis is regulated by the adaptive UPR pathway, which determines cell fate and maintains cell structure and function. The adaptive UPR pathway is regulated by 3 major ER stress sensors such as inositol-requiring protein 1 (IRE1), pancreatic eukaryotic translation initiation factor 2α (eIF-2α) kinase (PERK), and activating transcription factor 6 (ATF6). These transducers are inactive under normal conditions. When ER function is decreased under pathogenic conditions (ER stress), these transducers are activated by phosphorylation or cleavage in the Golgi apparatus; activate UPR transcription factors such as X-box-binding protein 1 (XBP1), ATF4, and cleaved ATF6; and then accelerate the expression of genes that function to maintain ER proteostasis (adaptive UPR pathway). PERK phosphorylates eIF2α to selectively increase the translation of ATF4 and inhibit global protein translation. When ER stress is severe or prolonged, the apoptotic UPR pathway associated with apoptosis-related gene expression, such as CEBP-homologous protein (CHOP), also is induced, eventually causing cell death, usually in the form of apoptosis. CEBP, CCAAT/enhancer binding protein.
Kidney International DOI: ( /j.kint )
Copyright © 2019 International Society of Nephrology Terms and Conditions

4. Figure 3
NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM). The MAM plays an important role in various signaling pathways that are essential for organelle crosstalk, especially that of the ER-mitochondria. For example, the MAM regulates inflammatory signals and NLRP3 inflammasome activation. Assembly of NLRP3 and apoptosis associated speck-like protein (ASC) occurs at the MAM; NLRP3 and ASC are localized mainly on the membrane of the ER and mitochondria, respectively. Damaged mitochondria express ASC, an adaptor that binds NLRP3 to initiate inflammasome signaling, which increases the frequency of regions of close proximity between the ER and mitochondria. Signaling from NLRP3 to ASC at the MAM promotes NLRP3 inflammasome activation, which is associated with the production of mature interleukin (IL)-1β/IL-18.
Kidney International DOI: ( /j.kint )
Copyright © 2019 International Society of Nephrology Terms and Conditions