| First Author | Shioda N | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 28 | Pages | 23318-31 |
| PubMed ID | 22619170 | Mgi Jnum | J:188867 |
| Mgi Id | MGI:5442474 | Doi | 10.1074/jbc.M112.349142 |
| Citation | Shioda N, et al. (2012) Expression of a truncated form of the endoplasmic reticulum chaperone protein, sigma1 receptor, promotes mitochondrial energy depletion and apoptosis. J Biol Chem 287(28):23318-31 |
| abstractText | The sigma1 receptor (sigma(1)R) regulates endoplasmic reticulum (ER)/mitochondrial interorganellar Ca(2+) mobilization through the inositol 1,4,5-trisphosphate receptor (IP(3)R). Here, we observed that expression of a novel splice variant of sigma(1)R, termed short form sigma(1)R (sigma(1)SR), has a detrimental effect on mitochondrial energy production and cell survival. sigma(1)SR mRNA lacks 47 ribonucleotides encoding exon 2, resulting in a frameshift and formation of a truncated receptor. sigma(1)SR localizes primarily in the ER at perinuclear regions and forms a complex with sigma(1)R but not with IP(3)R in the mitochondrion-associated ER membrane. Overexpression of both sigma(1)R and the truncated isoform promotes mitochondrial elongation with increased ER mitochondrial contact surface. sigma(1)R overexpression increases the efficiency of mitochondrial Ca(2+) uptake in response to IP(3)R-driven stimuli, whereas sigma(1)SR overexpression reduces it. Most importantly, sigma(1)R promotes ATP production via increased mitochondrial Ca(2+) uptake, promoting cell survival in the presence of ER stress. By contrast, sigma(1)SR suppresses ATP production following ER stress, enhancing cell death. Taken together, the newly identified sigma(1)SR isoform interferes with sigma(1)R function relevant to mitochondrial energy production under ER stress conditions, promoting cellular apoptosis. |
