The lipid basis of cell death and autophagy

ABSTRACT

Triglycerides, phospholipids, and cholesterol are prominent lipid types that serve diverse biological functions. These lipids act as vital structural components of cell membranes, provide energy for the body, and serve as signaling molecules that regulate physiological and pathological processes, including regulated cell death (RCD). While the initiation signals, biochemical pathways, and effector molecules may differ, increased membrane permeabilization from plasma membranes or organelles is a shared characteristic of RCD. This process involves alterations in lipid species and functions, along with autophagic degradation. Thus, the lipid hypothesis presents a novel perspective that complements other theories elucidating the features of cell survival and cell death. In this review, we present a comprehensive summary of the latest findings on the role and potential mechanisms of diverse lipids in influencing RCD processes, encompassing apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy.

Abbreviations

ACSL: acyl-CoA synthetase long chain family; DISC: death-inducing signaling complex; DAMPs: danger/damage-associated molecular patterns; Dtgn: dispersed trans-Golgi network; FAR1: fatty acyl-CoA reductase 1; GPX4: glutathione peroxidase 4; LPCAT3: lysophosphatidylcholine acyltransferase 3; LPS: lipopolysaccharide; MUFAs: monounsaturated fatty acids; MOMP: mitochondrial outer membrane permeabilization; MLKL, mixed lineage kinase domain like pseudokinase; oxPAPC: oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine; OxPCs: oxidized phosphatidylcholines; PUFAs: polyunsaturated fatty acids; POR: cytochrome p450 oxidoreductase; PUFAs: polyunsaturated fatty acids; RCD: regulated cell death; RIPK1: receptor interacting serine/threonine kinase 1; SPHK1: sphingosine kinase 1; SOAT1: sterol O-acyltransferase 1; SCP2: sterol carrier protein 2; SFAs: saturated fatty acids; SLC47A1: solute carrier family 47 member 1; SCD: stearoyl-CoA desaturase; VLCFA: very long chain fatty acids

KEYWORDS:

• Apoptosis
• autophagy
• cell death
• lipid metabolism
• pathway

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81974000, 82303255 and 82270185], the Natural Science Foundation of Hunan Province [2021JJ10077, 2023JJ40894 and 2023JJ40894] and the National Institutes of Health [GM131919].