Abstract
Despite peroxisomes being important partners of mitochondria by carrying out fatty acid oxidation in brown adipocytes, no clear evidence concerning peroxisome origin and way(s) of biogenesis exists. Herein we used methimazole-induced hypothyroidism for 7, 15, and 21 days to study peroxisomal remodeling and origin in rat brown adipocytes. We found that peroxisomes originated via both canonic, and de novo pathways. Each pathway operates in euthyroid control and over the course of hypothyroidism, in a time-dependent manner. Hypothyroidism increased the peroxisomal number by 1.8-, 3.6- and 5.8-fold on days 7, 15, and 21. Peroxisomal presence, their distribution, and their degree of maturation were heterogeneous in brown adipocytes in a Harlequin-like manner, reflecting differences in their origin. The canonic pathway, through numerous dumbbell-like and “pearls on strings” structures, supported by high levels of Pex11β and Drp1, prevailed on day 7. The de novo pathway of peroxisomal biogenesis started on day 15 and became dominant by day 21. The transition of peroxisomal biogenesis from canonic to the de novo pathway was driven by increased levels of Pex19, PMP70, Pex5S, and Pex26 and characterized by numerous tubular structures. Furthermore, specific peroxisomal origin from mitochondria, regardless of thyroid status, indicates their mutual regulation in rat brown adipocytes.
Highlights
Peroxisomes are highly dynamic organelles able to rapidly adapt to cellular metabolic requirements by changing their abundance, shape, size, and enzyme profile within [1]
We looked at the level of transcriptional regulation and analyzed the protein expression of the major transcription factors responsible for peroxisomal biogenesis, PPARα and PPARγ
Our results demonstrated the existence of this pathway in euthyroid brown adipocytes, which over the time course of hypothyroidism became the major way of peroxisomal biogenesis on day 7 and, to a lesser extent, on day 15
Summary
Peroxisomes are highly dynamic organelles able to rapidly adapt to cellular metabolic requirements by changing their abundance, shape, size, and enzyme profile within [1]. Peroxisomes perform various functions that differ depending on the species, organism, cell type, and environmental conditions. Peroxisomes are involved in lipid metabolism and their main function is β-oxidation of fatty acids [2]. Peroxisomal biogenesis has been well studied but gaps in our knowledge remain. De novo peroxisomal biogenesis is still illdefined [5]. Peroxisomes can originate de novo by “budding” from the smooth endoplasmic reticulum (sER). Recent studies indicated transport and communication between mitochondria and peroxisomes by mitochondria-derived vesicles [6]. Mohanty and McBride proposed that both ER and mitochondria-derived vesicles could contribute to peroxisomal biogenesis [7]. Whether peroxisomes can arise de novo from mitochondria in physiological or other pathological conditions and in vivo remains an open question
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