Organelle crosstalk in the kidney

Abstract

Organelle damage can cause various kidney diseases. In particular, organelle stress such as decreased proteostatic activity in the endoplasmic reticulum (ER) and altered energy metabolism in mitochondria contribute to glomerular and tubulointerstitial damage, resulting in the progression and development of kidney diseases. The ER regulates protein quality control via the unfolded protein response (UPR) pathway. Pathogenic ER stress leads to dysregulation of this pathway, and a maladaptive UPR is highly deleterious to renal cell function, and thereby has been implicated in the pathophysiology of various kidney diseases. The UPR pathway in the ER also regulates mitochondrial metabolic status, indicating the pathophysiological significance of organelle crosstalk between the ER and mitochondria via the UPR pathway. In recent years, it has become obvious that communication among organelles also is conducted through direct interactions at membrane contact sites (MCSs). Organelles exchange materials including lipids, ions, and proteins at the MCS. Accordingly, alterations to these networks, such as impaired ER-mitochondria MCSs, have been linked to several diseases such as neurodegeneration and diabetes. In this review, we describe the roles of organelles in kidney diseases and the mechanisms underlying organelle communication at the MCS, and especially at the mitochondria-associated ER membrane. Potential treatment options that are focused on organelle crosstalk are discussed, in addition to the relationship between this phenomenon and various diseases, especially kidney diseases.

Specific BK Channel Activator NS11021 Protects Rat Renal Proximal Tubular Cells from Cold Storage—Induced Mitochondrial Injury In Vitro

“…Interestingly, cardiac myocytes also do not express plasmalemmal BK channels, and NS11021 shows therapeutic efficacy against IR injury in these cells and in ex vivo models of cardiac IR [18,21,22]. Nevertheless, our studies did not rule out the possibility that NS11021 activates BK channels at other non-mitochondrial organelles considering that cross-talk between intracellular organelles is well recognized [69][70][71][72][73][74]. Indeed, BK channels have been discovered in many cellular organelles as is nicely reviewed by Sing et al [75].…”

Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress

“…In addition, other findings revealed that ER stress is involved in AKI triggered by renal I/R injury and nephrotoxic drugs (Gallazzini and Pallet, 2018;Yan et al, 2018). Many studies have reported that ER stress could trigger inflammatory responses and regulate mitochondrial metabolic status through the UPR signaling pathway (Bronner et al, 2015;So, 2018;Gallazzini and Pallet, 2018;Inoue et al, 2019). However, whether ER stress is involved in the protective effect of FGF2 on AKI has not yet been fully clarified.…”

“…Currently, the role of ER stress in the regulation of cell growth, cell migration, cell differentiation, and apoptosis has been confirmed. Many studies have shown the relationship between excessive activation of ER stress and various kidney diseases, including AKI, chronic kidney disease (CKD), glomerular disease, and diabetic nephropathy (Inoue et al, 2019). Apoptosis, a form of programed cell death characterized by DNA cleavage and nuclear condensation, has been observed and well recognized in AKI (Schumer et al, 1992;Linkermann et al, 2014).…”

Organelle Stress and Crosstalk in Kidney Disease

“…Peroxisome proliferator activated receptor gamma co-activator-1-α (PGC-1α), a mitochondrial biogenesis regulator, plays a pivotal role in proximal tubular recovery from acute kidney injury (AKI) by regulating nicotinamide adenine dinucleotide (NAD) biosynthesis 2 . Mitochondrial dysfunction in the proximal tubular cells after AKI results in the progression of chronic kidney disease (CKD) 3,4 .…”