A 45 kDa protein related to PPARγ2, induced by peroxisome proliferators, is located in the mitochondrial matrix

Abstract

Besides their involvement in the control of nuclear gene expression by activating several peroxisome proliferatoractivated receptors (PPARs), peroxisome proliferators influence mitochondrial activity. By analogy with the previous characterization of a mitochondrial T3 receptor (p43), we searched for the presence of a peroxisome proliferator target in the organelle. Using several antisera raised against different domains of PPARs, we demonstrated by Western blotting, immunoprecipitation and electron microscopy experiments, that a 45 kDa protein related to PPARQ Q2 (mt-PPAR) is located in the matrix of rat liver mitochondria. In addition, we found that the amounts of mt-PPAR are increased by clofibrate treatment. Moreover, in EMSA experiments mt-PPAR bound to a DR2 sequence located in the mitochondrial D-loop, by forming a complex with p43. Last, studies of tissue-specific expression indicated that mt-PPAR is detected in mitochondria of all tissues tested except the brain in amounts positively related to p43 abundance. ß

Altered cholesterologenic and lipogenic transcriptional profile in livers of aging Snell dwarf (Pit1dw/dwJ) mice

“…Peroxisome proliferators exert marked thyromimetic effects and are potent hypolipidaemic agents . In rats, peroxisome proliferators mediate the expression of genes regulated by thyroid hormone, including malic enzyme, mitochondrial glycerol-3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase and SPOT14 (Casas et al, 2000). The TSH deficiency of Pit1 dw/dwJ mice may also play a role in longevity determination owing to its function as a key regulator of various metabolic processes.…”

Steroid and thyroid hormone receptors in mitochondria

“…Thus, the retinoic acid receptor RAR (62), the retinoid receptor alpha (RXRa) (60), the orphan receptor Nur 77/ TR3 (63,64), and the PPAR b-and c2-coactivator (PPARb-and c 2 ) related proteins (65) have been localized in mitochondria (Table 1). Among the nuclear transcription factors found in mitochondria are NF-jB, AP-1, CREB, p53, c-myc, wnt 13, Dok-4, HMG-A1, and c-src (reviewed in refs.…”

Regulation of Mitochondrial Gene Expression by Retinoids

“…However, not all of the data support this theory and researchers have observed RARs outside of the nucleus (32). Receptors for thyroid (33), glucocorticoid (34-36), estradiol (37), and peroxisome proliferators (38) have been shown to localize to mitochondria. The two thyroid receptors found in the mt are truncated forms.…”

“…This might suggest that additional factors are required for this DR2 to respond to thyroid hormone. Casas et al (38) reported that a truncated PPAR γ 2-like protein (mt-PPAR) bound this DR2 in a complex with TR/p43. This element has also been shown to act as a RARE in other genes (46 ).…”