The role of Mitochondrial Fission Proteins in Mitochondrial Dynamics in Kidney Disease

Abstract

Mitochondria have many forms and can change their shape through fusion and fission of the outer and inner membranes, called “mitochondrial dynamics”. Mitochondrial outer membrane proteins, such as mitochondrial fission protein 1 (FIS1), mitochondrial fission factor (MFF), mitochondrial 98 dynamics proteins of 49 kDa (MiD49), and mitochondrial dynamics proteins of 51 kDa (MiD51), can aggregate at the outer mitochondrial membrane and thus attract Dynamin-related protein 1 (DRP1) from the cytoplasm to the outer mitochondrial membrane, where DRP1 can perform a scissor-like function to cut a complete mitochondrion into two separate mitochondria. Other organelles can promote mitochondrial fission alongside mitochondria. FIS1 plays an important role in mitochondrial–lysosomal contacts, differentiating itself from other mitochondrial-fission-associated proteins. The contact between the two can also induce asymmetric mitochondrial fission. The kidney is a mitochondria-rich organ, requiring large amounts of mitochondria to produce energy for blood circulation and waste elimination. Pathological increases in mitochondrial fission can lead to kidney damage that can be ameliorated by suppressing their excessive fission. This article reviews the current knowledge on the key role of mitochondrial-fission-associated proteins in the pathogenesis of kidney injury and the role of their various post-translational modifications in activation or degradation of fission-associated proteins and targeted drug therapy.

Drp1-JNKknockdown mitigates Scribble loss induced cell proliferation, metastasis and lethality phenotypes inDrosophila

“…Overall, Scrib plays a role in maintaining the cell polarity and cell proliferation regulation by blocking the Drp1 and JNK which regulate mitochondrial dynamics, via maintaining the mitochondrial membrane polarity, morphology and oxidative stress. Mitochondria, a dynamic double membrane-bound cell organelles, play crucial role in ATP production, recently emerged as hub for Drp-1 mediated mitochondrial fission protein interactome connective pathways for various diseases [50]. Our results clearly show that upon knockdown of Scrib leads to enhanced Drp-1 mediated disruption of mitochondrial dynamics, which induces enhanced ROS production and cause reduced ATP production leading to increased cell proliferation and metastasis.…”

Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury

“…During AKI, a redundant fission of mitochondria occurs, accompanied by the expression of mitochondrial fission 1 protein (FIS1) and Drp1 [ 48 ]. The inhibition of mitochondrial fragmentation prevents the progression of AKI to CKD [ 49 ]. That is why we assessed mitochondrial dynamics and analyzed the effects of sex and hormone treatment to them.…”

The Janus-faced functions of Apolipoproteins L in membrane dynamics

“…Changes in surface membrane dynamics could trigger effacement of podocyte foot processes and consecutive impairment of kidney activity. Kidney function is also particularly affected by interference with mitochondrial membrane fission [82], which reduces IFN-I-induced mitophagy and leads to mitochondrion dysfunctions together with exacerbated inflammatory reaction. Both effects on actomyosin organization and auto/mitophagy flux are characteristic of APOL1 variants-linked kidney disease, either genuine in humans or transgenic in mice or Drosophila melanogaster lines [10,11,83].…”