Center for Electron Microscopy, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia.
Department of Physiology, Institute for Biological Research "Sinisa Stankovic"-National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
Cells. 2021 Aug 30;10(9):2248. doi: 10.3390/cells10092248.
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 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 pathway of peroxisomal biogenesis started on day 15 and became dominant by day 21. The transition of peroxisomal biogenesis from canonic to the 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.
尽管过氧化物酶体通过在棕色脂肪细胞中进行脂肪酸氧化来成为线粒体的重要伙伴，但关于过氧化物酶体的起源和生物发生途径仍没有明确的证据。在此，我们使用甲巯咪唑诱导的甲状腺功能减退症来研究大鼠棕色脂肪细胞中过氧化物酶体的重塑和起源，为期 7、15 和 21 天。我们发现过氧化物酶体通过经典途径和非经典途径起源。这两种途径在甲状腺功能正常的对照和甲状腺功能减退症期间都以时间依赖的方式运作。甲状腺功能减退症使过氧化物酶体的数量在第 7、15 和 21 天分别增加了 1.8 倍、3.6 倍和 5.8 倍。过氧化物酶体在棕色脂肪细胞中的存在、分布和成熟程度呈 Harlequin 样不均一性，反映了它们起源的差异。经典途径通过大量哑铃状和“串珠”结构，由高水平的 Pex11β 和 Drp1 支持，在第 7 天占主导地位。过氧化物酶体生物发生的非经典途径始于第 15 天，并在第 21 天成为主导途径。过氧化物酶体生物发生从经典途径向非经典途径的转变是由 Pex19、PMP70、Pex5S 和 Pex26 水平的增加驱动的，其特征是存在大量管状结构。此外，无论甲状腺状态如何，棕色脂肪细胞中过氧化物酶体的特定起源都表明它们之间存在相互调节。
