Page 115 - 南京医科大学自然版

第46卷第9期 王振涛，张凯妮，苏东明. 脂滴⁃线粒体接触点在肝脏代谢障碍与缺血再灌注损伤中的研究进展［J］.
2026年9月 南京医科大学学报（自然科学版），2026，46（9）：1383-1397 ·1385 ·

三元互作网络中（图1）。 粒体融合⁃分裂平衡及细胞代谢状态共同形成的动
线粒体动力学状态也是决定接触点稳定性的 态结构。
关键因素。Boutant 等 ［12］ 在棕色脂肪组织中的研究 这一接触点的生理意义，首先体现在脂肪酸的
证实，线粒体融合蛋白 2（mitofusin 2，MFN2）可直接 利用上。长链脂肪酸自脂滴动员后，需要在线粒体
与脂滴包被蛋白相互作用，促进线粒体与脂滴之间 外膜附近迅速被活化并导入β⁃氧化通路。Coleman
的贴附，从而影响脂解产物的利用效率。Rambold 等 ［14］ 提 出 ，长 链 脂 酰 辅 酶 A 合 成 酶 1（acyl ⁃ CoA
等 ［13］ 进一步指出，在饥饿状态下，脂滴来源脂肪酸 synthetase long⁃chain family member 1，ACSL1）并非
向线粒体的有效转运依赖于线粒体保持较高的融 孤立发挥作用，而是处于由线粒体外膜、脂滴和相
合状态；当融合受损时，脂肪酸难以被线粒体均匀 关栓系蛋白共同构成的代谢互作网络中，从而提高
利用，反而可能重新回流至脂滴或转运至邻近细胞 脂酰辅酶A生成及后续代谢效率。Lee 等 ［15］ 进一步
器。上述结果提示，脂滴⁃线粒体接触点的形成并非 证实，肝线粒体外膜上的肉碱棕榈酰转移酶 1a
单纯由某一个“桥接蛋白”决定，而是蛋白栓系、线 （carnitine palmitoyltransferase 1a，CPT1a）可与ACSL和

1. Modes of contact Central main body 2. Tethering molecules and structural regulators
Dynamic/reversible Anchored/stable Endoplasmic
contact contact reticulum
Localized on core PLIN5
Neutral bridging protein of （ER）
bridging LD & mitochondria MIGA2
protein
LD
LD
LD
Mitochondria MFN2
drnamics
Phospholipid
monolayer
Local
apposition
3. Mitochondrial dynamics and contact stability 4. Functional heterogeneity of mitochondria
Mitochondrial Mitochondrial ACSL1 Peridroplet mitochondria（PDM）/ Cytosolic
fusion Mitochondrial fragmentation CPT1a VDAC LD⁃associated mitochondria mitochondria
network fusion tightly apposed；capture distal to LD
LD⁃mitochondria distinct proteome as control
contact site PDM
LD
Directional Redox
fatty acid homeostasis
Mitochondrial fusion transfer ATP Peridroplet mitochondria（PDM）/
supports effective Energy Cytosolic
Efficient Impaired allocation β⁃oxidation production LD⁃associated mitochondria mitochondria
FA trafficking
FA utilization FA distribution efficiency Stress response focus at capture and local distal to LD control
integration metabolic coupling
LD （Acyl⁃CoA synthetase long⁃ （Carnitine （Voltage⁃dependent PLIN5 MIGA2 MFN2
（lipid droplet） Mitochondria ACSL1 chain farnily member 1） CPT1a palmitoyltransferase 1 a） VDAC anion channel） （perilipin 5） （mitoguardin 2） （mitofusin 2）
The diagram illustrates the main structural pattern，molecular composition，and functional output of the lipid droplet mitochondrial contact point.
Lipid droplets can form dynamic reversible contact or relatively stable anchoring contact with mitochondria，and their stability is regulated by
mitochondrial fusion/fission status and local tethering molecules. PLIN5，MIGA2，MFN2，and other molecules participate in the structural connections
between lipid droplets，mitochondria and endoplasmic reticulum，while ACSL1，CPT1a，and VDAC participate in fatty acid activation，transport and
mitochondrial uptake. Different mitochondrial subgroups exhibit heterogeneity in function，with lipid droplet associated mitochondria more inclined to
participate in local fatty acid oxidation and metabolic coupling，while cytoplasmic mitochondria can serve as a control group relatively distant from lipid
droplets. Overall，the lipid droplet mitochondrial contact point forms an important structural basis for regulating lipid fate and mitochondrial stress
response by coordinating fatty acid transport，beta oxidation，ATP generation，and redox homeostasis. LD：lipid droplet；ER：endoplasmic reticulum；
PLIN5：perilipin 5；MIGA2：mitoguardin 2；MFN2：mitofusin 2；ACSL1：acyl CoA synthase long chain family member 1；CPT1a：carnitine
palmitoyltransferase 1a；VDAC：voltage dependent anion channel；PDM：peridroplet mitochondria；CM：cytoplasmic mitochondria；FA：fatty acids；ATP：
adenosine triphosphate.
图1 脂滴⁃线粒体接触点的结构基础与关键分子网络
Figure 1 Structural basis and key molecular network of lipid droplet⁃mitochondria contact sites