Ubiquitination of Mfn2 by MITOL may hamper ER mitochondria interactions selleck screening library at the mitochondria associated membranes [60]. MITOL has also been shown to ubiquitinate Drp1, hFis1, and mutant SOD1 [61]. Blocking the proteasome causes accumulation of intermembrane space proteins like EndonucleaseG (EndoG). Ubiquitination of these proteins occurs prior to import into the organelle as deletion of the mitochondrial targeting sequence does not affect ubiquitination. On proteasome inhibition, the intermembrane space protease Omi/Htra1 cleaves endoG acting as a backup mechanism of protein quality control in the mitochondria when the proteasomal system is malfunctioning [62]. Deubiquitinating enzymes like Ubiquitin-specific processing protease 16 (Ubp16) have also been discovered to be present on the mitochondrial outer membrane [63].

Though most of these are mitochondrial outer membrane proteins, many matrix resident proteins are also ubiquitinated by the cytosolic UPS. A recent proteomic study has identified a wide array of interactors for the cytosolic E3 ligase PARKIN; along with cytosolic and nuclear molecular partners, surprisingly, there are also proteins of the mitochondrial matrix [64]. How the proteasomal machinery gets access to the proteins residing inside the mitochondria remains uncertain. Whether the proteasomal components are recruited to the mitochondria or other ancillary proteins extract the membrane proteins from the mitochondrial membrane and transport them to the proteasome is unknown [57]. Recent reports indicate the presence of
AKI is defined as a sudden decrease in kidney function.

AKI is one of the serious conditions that affect the structure and function of kidneys. It is a broad clinical syndrome, including specific diseases affecting the kidney such as MM. Even a minor acute reduction in kidney function correlates to an adverse prognosis. A schematic view of the conceivable course of AKI has been proposed (Figure 2) [19]. AKI could be an important cause of CKD or ESRD. Therefore, early detection and treatment of AKI would improve outcomes. Two criteria of AKI, which were based on sCr and urine output, the Risk, Injury, Failure, Loss, End-Stage Renal Disease (RIFLE) [21] and Acute Kidney Injury Network (AKIN) [22] have been proposed and validated. Recently, severity of AKI staged by RIFLE criteria (OR = 2.

04 Failure stages versus Risk and Injury stage P = 0.06) has been reported as associated with marginally better long-term outcome in MM patients [23]. In 2012, the Kidney Disease: Improving Global Outcomes (KDIGO) AKI Guideline Work Group accepted the existing criteria for the diagnosis and staging of AV-951 AKI and proposed a single definition of AKI that should be useful for practice, research, and public health (Table 3) [20].