High impact information on FIS1

• In addition, overexpression phenotype of hFis1 could be reverted by MITOL co-overexpression [1].
• These morphological changes in mitochondria have been shown to require proteins, such as Drp1 or hFis1, which are involved in regulating the fission of mitochondria [2].
• These studies indicate that mitofusins and OPA1 are essential for mitochondrial fusion, whereas Fis1 and Drp1 are essential for mitochondrial fission [3].
• Remarkably, an increased level of cellular hFis1 strongly promotes mitochondrial fission, resulting in an accumulation of fragmented mitochondria [4].
• Further, fluorescence resonance energy transfer and coimmunoprecipitation studies demonstrate that hFis1 interacts with DLP1 [4].

Biological context of FIS1

• Cells depleted of Opa1 are extremely sensitive to exogenous apoptosis induction, and some die spontaneously by a process that requires hFis1 expression [5].
• Down-regulation of hFis1 powerfully inhibits cell death to an extent significantly greater than down-regulation of Drp1 and at a stage of apoptosis distinct from that induced by Drp1 inhibition [5].
• Knockdown of hFis1 in COS-7 cells using RNA interference results in mitochondrial morphology defects with notable extensions in the length of mitochondrial tubules [6].
• Although expression of hFis1 does not complement the phenotype of yeast cells lacking Fis1p, overexpression of hFis1 in tissue culture cells nevertheless causes mitochondrial fragmentation and aggregation [6].
• Ca(2+) homeostasis during mitochondrial fragmentation and perinuclear clustering induced by hFis1 [7].

Anatomical context of FIS1

• We show that hFis1 localizes to peroxisomes in addition to mitochondria [8].
• In this study we have identified a mammalian protein that we call hFis1, which is the orthologue of the yeast Fis1p known to participate in yeast mitochondrial division. hFis1, when overexpressed in various cell types, localized to the outer mitochondrial membrane and induced mitochondrial fission [9].
• In contrast, hFis1-fragmented mitochondria took up more slowly the Ca(2+) entering across plasma membrane channels, because the Ca(2+) ions reaching mitochondria propagated faster and in a more coordinated manner in interconnected than in fragmented mitochondria [7].
• Special emphasis is on the function of dynamin-related proteins (DRPs), on Fis1, a putative adaptor for DRPs, on the role of the Pex11 family of peroxisomal membrane proteins, and the cytoskeleton [10].

Associations of FIS1 with chemical compounds

• Upon Ca2+ withdrawal, the free ER Ca2+ concentration decreased rapidly, and hFis1 cells were unable to respond to repetitive histamine stimulations [11].
• In the stable hFis1 knockdown cells, hFis1 expression was suppressed to approximately 10%, and mitochondrial fission, induced by cisplatin treatment, was delayed [12].
• A rust-inducible gene from flax (fis1) is involved in proline catabolism [13].
• The fis1 gene has 73% homology with an Arabidopsis gene which encodes delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDH) which is a part of the proline degradation pathway [13].

Other interactions of FIS1

• The yeast protein Fis1p has been shown to participate in mitochondrial fission mediated by the dynamin-related protein Dnm1p [4].
• Moreover, MTP18 appears to be required for mitochondrial fission because it is blocked after overexpression of hFis1 in cells with RNAi-mediated MTP18 knockdown [14].
• Cytosolic domain of the human mitochondrial fission protein fis1 adopts a TPR fold [15].
• We also showed that GD3, the voltage-dependent anion channel-1 (VDAC-1) and the fission protein hFis1 are structural components of a multimolecular signaling complex, in which Bcl-2 family proteins (t-Bid and Bax) are recruited [16].
• Silencing of Pex19p by small interference RNA reduced the targeting of hFis1 to peroxisomes, but not to mitochondria [17].

Analytical, diagnostic and therapeutic context of FIS1

• Conversely, cell microinjection of hFis1 antibodies or treatment with hFis1 antisense oligonucleotides induces an elongated and collapsed mitochondrial morphology [4].

References