Comparative proteomics reveals that lipid droplet-anchored mitochondria are more sensitive to cold in brown adipocytes

Ahmed Hammad Mirza; Liujuan Cui; Shuyan Zhang; Pingsheng Liu

doi:10.1016/j.bbalip.2021.158992

Comparative proteomics reveals that lipid droplet-anchored mitochondria are more sensitive to cold in brown adipocytes

Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Oct;1866(10):158992. doi: 10.1016/j.bbalip.2021.158992. Epub 2021 Jun 17.

Authors

Ahmed Hammad Mirza¹, Liujuan Cui², Shuyan Zhang³, Pingsheng Liu⁴

Affiliations

¹ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
³ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: syzhang@ibp.ac.cn.
⁴ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: pliu@ibp.ac.cn.

PMID: 34147658
DOI: 10.1016/j.bbalip.2021.158992

Abstract

Brown adipose tissue (BAT) is specialized for uncoupled heat production through mitochondrion fueled majorly from fatty acids (FAs) of lipid droplets (LDs). How the interaction between the two organelles contributes the generation of heat remains elusive. Here, we report that LD-anchored mitochondria (LDAM) were observed in the BAT of mice raised at three different temperatures, 30 °C, 23 °C, and 6 °C. The biochemical analyses including Western blotting of electron transport chain subunits showed that LDAM were functional. Comparative proteomics analysis was conducted, which revealed differential expressions of proteins between LDAM and cytoplasmic mitochondria (CM) at different temperatures. Higher expressions of proteins at low temperature were observed for i) FA β-oxidation in LDAM including FA synthesis and uncoupling, ii) pseudo-futile cycle in CM, and iii) two shuttle systems: glycerol 3-phosphate in both CM and LDAM and citrate malate in CM. Together, these results suggest that LDs and LDAM form a preorganized and functional organelle complex that permits the rapid response to cold.

Keywords: BAT; Comparative proteomics; FA β-oxidation; Lipid droplet-anchored mitochondria.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes, Brown / cytology
Adipocytes, Brown / metabolism*
Adipocytes, Brown / ultrastructure
Adipose Tissue, Brown / cytology
Adipose Tissue, Brown / metabolism
Adipose Tissue, Brown / ultrastructure
Animals
CD36 Antigens / metabolism
Cell Fractionation
Cell Separation
Cold Temperature / adverse effects*
Energy Metabolism / genetics*
Fatty Acids / metabolism
Gene Expression Regulation
Lipid Droplets / metabolism*
Lipid Droplets / ultrastructure
Lipid Metabolism / genetics
Male
Mice
Microscopy, Electron, Transmission
Mitochondria / metabolism*
Mitochondria / ultrastructure
Oxidation-Reduction
Proteomics
Vesicular Transport Proteins / metabolism

Substances

CD36 Antigens
Fatty Acids
Vesicular Transport Proteins
Vps13a protein, mouse