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Intimacy and a deadly feud: the interplay of autophagy and apoptosis mediated by amino acids

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Abstract

Autophagy (i.e., “self-eating”) and apoptosis (i.e., type I programmed cell death) are essential and intimately involved in molecular, cellular, and whole-body homeostasis in humans and animals. Autophagy has been categorized as a mechanism of intracellular degradation, recycling, defense, and survival. To date, three types of autophagy have been identified: macroautophagy, microautophagy, and chaperone-mediated autophagy. Recent discoveries strongly suggest that macroautophagy also modulates type II programmed cell death under specific circumstances. Autophagy and apoptosis are fundamentally distinct processes, but are interconnected by common stress initiators and intermediate regulators. During the past two decades, the role of amino acid metabolism and signaling in the regulation of apoptosis and autophagy has been intensively studied. In this review, we summarize recent advances in our understanding of the molecular mechanisms that regulate both autophagy and apoptosis in the context of amino acid signaling.

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Abbreviations

AIF:

Apoptosis-inducing factor

AMBRA1:

Activating molecule in BECN1-regulated autophagy protein 1

AMPK:

AMP-activated protein kinase

Apaf-1:

Apoptotic protease-activating factor-1

ApoL6:

Apolipoprotein L6

Atg:

Autophagy-related gene

BAD:

Bcl-2-associated death protein

Bcl-2:

B cell lymphoma 2

Beclin 1:

Bcl-2 interacting protein 1

Bfl-1:

Bcl-2-related gene expressed in fetal liver

BH3:

Bcl-2-homology-3 domain

BH:

Bcl-2 homology

BID:

BH3 interacting-domain death agonist

Bif-1:

Bax-interacting factor-1

DAPK:

Death-associated protein kinase

DISC:

Death-inducing signaling complex

DRAM:

Damage-regulated autophagy modulator

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated kinase

FADD:

FAS-associated death domain protein

FLICE:

FADD-like interleukin-1 β-converting enzyme

FIP200:

Focal adhesion kinase family-interacting protein of 200 kDa

hVps34:

Human vacuolar protein sorting-34

IAPs:

Inhibitors of apoptosis proteins

IGF-1:

Insulin-like growth factor-1

IRS:

Insulin receptor substrate

JNK:

c-Jun N-terminal kinase

LC3:

Microtubule-associated protein 1 light chain 3

MAPK:

Mitogen-activated protein kinase

MOMP:

Mitochondrial outer membrane permeabilization

mTOR:

Mammalian target of rapamycin

PCD:

Programmed cell death

PI3K:

Phosphoinositide 3-kinase

ROS:

Reactive oxygen species

PRAS40:

Proline-rich AKT substrate of 40 kDa

SMAC:

Second mitochondrial-derived activator of caspase

TIGAR:

TP53-inducible glycolysis and apoptosis regulator

TNF-α:

Tumor necrosis factor-α

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

TSC1/2:

Tuberous sclerosis complex1/2

ULK1:

unc-51-like autophagy activating kinase 1

UVRAG:

Ultraviolet irradiation resistance-associated gene

SLC38A9:

Member 9 of the solute carrier family 38

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Acknowledgments

This work was supported by the National Institute of Health (5RO1CA106644 to CAAH), the National Key Basic Research Program of China (2013CB127302 to Z.W. and G.W.), and the Natural Science Foundation of China (31172217, 31272450, and 31272451 to Z.W. and G.W.), the Chinese Universities Scientific Fund (2013RC002), the Program for New Century Excellent Talents in University (NCET-12-0522), and the Program for Beijing Municipal Excellent Talents, the Agriculture and Food Research Initiative Competitive Grant from the USDA National Institute of Food and Agriculture (No. 2014-67015-21770), and Texas A&M AgriLife Research (H-8200).

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    1. State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People’s Republic of China

      Zhenlong Wu, Guoyao Wu, Kaiji Sun, Yun Ji, Bin Wang & Zhaolai Dai

    2. Department of Biochemistry and Molecular Biology, Health Sciences Center, University of New Mexico, Albuquerque, NM, 87131, USA

      Chien-An A. Hu

    3. Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University, Wuhan, 430023, People’s Republic of China

      Chien-An A. Hu, Guoyao Wu & Yongqing Hou

    4. Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA

      Guoyao Wu

    5. Division of Cardiology, Texas Heart Institute, Houston, TX, USA, 77030

      Siqin Zhaorigetu & Brian Walton

    6. Lovelace Respiratory Research Institute, Albuquerque, NM, USA, 87108

      Hitendra Chand

    7. Department of Radiology, University of Colorado Health Sciences Center, Denver, CO, 80262, USA

      Yubin Miao

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    1. Zhenlong Wu
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    Zhenlong Wu and Chien-An A. Hu have equally contributed.

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    Wu, Z., Hu, CA.A., Wu, G. et al. Intimacy and a deadly feud: the interplay of autophagy and apoptosis mediated by amino acids. Amino Acids 47, 2089–2099 (2015). https://doi.org/10.1007/s00726-015-2084-0

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