The concept of intrinsic versus extrinsic apoptosis

Regulated cell death is a vital and dynamic process in multicellular organisms that maintains tissue homeostasis and eliminates potentially dangerous cells. Apoptosis, one of the better-known forms of regulated cell death, is activated when cell-surface death receptors like Fas are engaged by their...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Biochemical journal Jg. 479; H. 3; S. 357
1. Verfasser: Lossi, Laura
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 11.02.2022
Schlagworte:
ISSN:1470-8728, 1470-8728
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Abstract Regulated cell death is a vital and dynamic process in multicellular organisms that maintains tissue homeostasis and eliminates potentially dangerous cells. Apoptosis, one of the better-known forms of regulated cell death, is activated when cell-surface death receptors like Fas are engaged by their ligands (the extrinsic pathway) or when BCL-2-family pro-apoptotic proteins cause the permeabilization of the mitochondrial outer membrane (the intrinsic pathway). Both the intrinsic and extrinsic pathways of apoptosis lead to the activation of a family of proteases, the caspases, which are responsible for the final cell demise in the so-called execution phase of apoptosis. In this review, I will first discuss the most common types of regulated cell death on a morphological basis. I will then consider in detail the molecular pathways of intrinsic and extrinsic apoptosis, discussing how they are activated in response to specific stimuli and are sometimes overlapping. In-depth knowledge of the cellular mechanisms of apoptosis is becoming more and more important not only in the field of cellular and molecular biology but also for its translational potential in several pathologies, including neurodegeneration and cancer.
AbstractList Regulated cell death is a vital and dynamic process in multicellular organisms that maintains tissue homeostasis and eliminates potentially dangerous cells. Apoptosis, one of the better-known forms of regulated cell death, is activated when cell-surface death receptors like Fas are engaged by their ligands (the extrinsic pathway) or when BCL-2-family pro-apoptotic proteins cause the permeabilization of the mitochondrial outer membrane (the intrinsic pathway). Both the intrinsic and extrinsic pathways of apoptosis lead to the activation of a family of proteases, the caspases, which are responsible for the final cell demise in the so-called execution phase of apoptosis. In this review, I will first discuss the most common types of regulated cell death on a morphological basis. I will then consider in detail the molecular pathways of intrinsic and extrinsic apoptosis, discussing how they are activated in response to specific stimuli and are sometimes overlapping. In-depth knowledge of the cellular mechanisms of apoptosis is becoming more and more important not only in the field of cellular and molecular biology but also for its translational potential in several pathologies, including neurodegeneration and cancer.Regulated cell death is a vital and dynamic process in multicellular organisms that maintains tissue homeostasis and eliminates potentially dangerous cells. Apoptosis, one of the better-known forms of regulated cell death, is activated when cell-surface death receptors like Fas are engaged by their ligands (the extrinsic pathway) or when BCL-2-family pro-apoptotic proteins cause the permeabilization of the mitochondrial outer membrane (the intrinsic pathway). Both the intrinsic and extrinsic pathways of apoptosis lead to the activation of a family of proteases, the caspases, which are responsible for the final cell demise in the so-called execution phase of apoptosis. In this review, I will first discuss the most common types of regulated cell death on a morphological basis. I will then consider in detail the molecular pathways of intrinsic and extrinsic apoptosis, discussing how they are activated in response to specific stimuli and are sometimes overlapping. In-depth knowledge of the cellular mechanisms of apoptosis is becoming more and more important not only in the field of cellular and molecular biology but also for its translational potential in several pathologies, including neurodegeneration and cancer.
Regulated cell death is a vital and dynamic process in multicellular organisms that maintains tissue homeostasis and eliminates potentially dangerous cells. Apoptosis, one of the better-known forms of regulated cell death, is activated when cell-surface death receptors like Fas are engaged by their ligands (the extrinsic pathway) or when BCL-2-family pro-apoptotic proteins cause the permeabilization of the mitochondrial outer membrane (the intrinsic pathway). Both the intrinsic and extrinsic pathways of apoptosis lead to the activation of a family of proteases, the caspases, which are responsible for the final cell demise in the so-called execution phase of apoptosis. In this review, I will first discuss the most common types of regulated cell death on a morphological basis. I will then consider in detail the molecular pathways of intrinsic and extrinsic apoptosis, discussing how they are activated in response to specific stimuli and are sometimes overlapping. In-depth knowledge of the cellular mechanisms of apoptosis is becoming more and more important not only in the field of cellular and molecular biology but also for its translational potential in several pathologies, including neurodegeneration and cancer.
Author Lossi, Laura
Author_xml – sequence: 1
  givenname: Laura
  orcidid: 0000-0003-1149-212X
  surname: Lossi
  fullname: Lossi, Laura
  organization: Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, I-10095 Grugliasco, Torino, Italy
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35147165$$D View this record in MEDLINE/PubMed
BookMark eNpNj8tLxDAYxIOsuA89eZcevVTzfXk0PWpZXyx4Wc-lTb9ipJvUphX9711wFzzNMPNjYJZs5oMnxi6B3wCXeHtfvCBH4EbJE7YAmfHUZGhm__ycLWP84Bwkl_yMzYXaV6DVgontOyU2eEv9mIQ2cX4cnI_OJl80xCkm9H0Mqj70Y4gunrPTtuoiXRx0xd4e1tviKd28Pj4Xd5vUCqXGlIzUvCEgLYURQDnWkEFDVZ0pDXkjZG1lQ6IGpSxogxkoo7DlSlQoiHDFrv92-yF8ThTHcueipa6rPIUplqjRYJ5zFHv06oBO9Y6ash_crhp-yuNR_AUfKFSb
CitedBy_id crossref_primary_10_1007_s10534_025_00742_1
crossref_primary_10_1016_j_jff_2024_106498
crossref_primary_10_3389_fcell_2025_1611936
crossref_primary_10_3390_ijms252111713
crossref_primary_10_1007_s10989_022_10458_2
crossref_primary_10_1016_j_biopha_2023_115990
crossref_primary_10_1016_j_phymed_2025_156743
crossref_primary_10_1016_j_semcdb_2024_01_006
crossref_primary_10_3892_etm_2025_12861
crossref_primary_10_1007_s00726_023_03373_3
crossref_primary_10_3389_fceld_2023_1281137
crossref_primary_10_3390_cimb46110748
crossref_primary_10_3390_molecules28207209
crossref_primary_10_1016_j_ejphar_2025_177349
crossref_primary_10_1016_j_intimp_2024_112240
crossref_primary_10_1177_1934578X251344985
crossref_primary_10_3390_foods13213508
crossref_primary_10_1242_jcs_260790
crossref_primary_10_2147_JIR_S514309
crossref_primary_10_1016_j_conb_2022_102629
crossref_primary_10_1016_j_taap_2025_117403
crossref_primary_10_3390_ani14203009
crossref_primary_10_1002_cmdc_202300519
crossref_primary_10_3390_ijms24076014
crossref_primary_10_1097_JCMA_0000000000000806
crossref_primary_10_3390_cancers16050885
crossref_primary_10_1016_j_mcn_2025_104016
crossref_primary_10_1038_s41598_024_66367_5
crossref_primary_10_3389_fphar_2025_1599756
crossref_primary_10_3390_molecules27196401
crossref_primary_10_3390_ani15020228
crossref_primary_10_1007_s11356_022_24213_z
crossref_primary_10_1021_acs_est_5c05893
crossref_primary_10_1186_s43094_025_00788_5
crossref_primary_10_1016_j_semcdb_2022_11_007
crossref_primary_10_3390_ph17010121
crossref_primary_10_1016_j_jtos_2024_11_004
crossref_primary_10_1155_cmi_7344471
crossref_primary_10_3389_fonc_2022_835027
crossref_primary_10_3892_ijmm_2023_5309
crossref_primary_10_1016_j_gene_2025_149270
crossref_primary_10_1038_s41598_025_97633_9
crossref_primary_10_3390_molecules28176208
crossref_primary_10_3390_molecules28041879
crossref_primary_10_1002_jbt_70373
crossref_primary_10_1002_mco2_693
crossref_primary_10_1016_j_fsi_2025_110687
crossref_primary_10_4014_jmb_2409_09025
crossref_primary_10_1002_vms3_70216
crossref_primary_10_1111_eci_14226
crossref_primary_10_1002_JLB_4MR0422_636R
crossref_primary_10_1016_j_watbs_2025_100409
crossref_primary_10_3390_encyclopedia2040111
crossref_primary_10_1016_j_biopha_2025_118363
crossref_primary_10_1007_s10495_025_02161_6
crossref_primary_10_1080_14786419_2023_2298383
crossref_primary_10_1016_j_bioorg_2025_108432
crossref_primary_10_1016_j_prp_2023_154889
crossref_primary_10_1021_acsnano_4c14273
crossref_primary_10_3390_cells13020183
crossref_primary_10_3390_cells12182304
crossref_primary_10_1515_jtim_2025_0004
crossref_primary_10_3390_genes15020183
crossref_primary_10_1113_JP287635
crossref_primary_10_1111_boc_202400077
crossref_primary_10_1002_tox_24515
crossref_primary_10_1007_s12013_023_01179_4
crossref_primary_10_1016_j_heares_2025_109287
crossref_primary_10_62347_NCFF5626
crossref_primary_10_3390_ijms26188876
crossref_primary_10_1016_j_tips_2025_05_002
crossref_primary_10_1080_15476286_2025_2525886
crossref_primary_10_1002_ptr_8128
crossref_primary_10_3390_ani14233394
crossref_primary_10_1016_j_heliyon_2024_e35636
crossref_primary_10_3892_or_2024_8771
crossref_primary_10_1007_s40291_023_00672_z
crossref_primary_10_1007_s10904_025_03901_6
crossref_primary_10_1002_jat_4536
crossref_primary_10_1016_j_scitotenv_2024_172125
crossref_primary_10_1515_oncologie_2024_0378
crossref_primary_10_1016_j_ccr_2025_217119
crossref_primary_10_1007_s11033_025_10924_2
crossref_primary_10_1016_j_omtn_2025_102649
crossref_primary_10_31083_j_fbl2904157
crossref_primary_10_1038_s41420_024_01978_5
crossref_primary_10_3389_fvets_2024_1360878
crossref_primary_10_4103_NRR_NRR_D_24_01324
crossref_primary_10_3390_pathogens12060839
crossref_primary_10_3390_pharmaceutics16121504
crossref_primary_10_1016_j_toxicon_2024_107718
crossref_primary_10_1038_s41418_023_01249_3
crossref_primary_10_2174_0109298673288774240406053607
crossref_primary_10_3390_biology12030415
crossref_primary_10_3390_ijms232315186
crossref_primary_10_1007_s12032_025_02762_w
crossref_primary_10_1016_j_bioorg_2025_108211
crossref_primary_10_1016_j_heliyon_2024_e37196
crossref_primary_10_1016_j_exer_2023_109728
crossref_primary_10_3390_cells14151203
crossref_primary_10_1007_s12032_023_02180_w
crossref_primary_10_3390_biom13060912
crossref_primary_10_3390_ijms241713527
crossref_primary_10_1016_j_arabjc_2024_105694
crossref_primary_10_1134_S1068162024030166
crossref_primary_10_1016_j_bbadis_2023_166720
crossref_primary_10_1016_j_bcp_2024_116588
crossref_primary_10_1016_j_bcp_2024_116621
crossref_primary_10_34133_bmr_0157
crossref_primary_10_1007_s10495_025_02081_5
crossref_primary_10_3390_ijms26104870
crossref_primary_10_1016_j_freeradbiomed_2024_04_235
crossref_primary_10_1016_j_ejmech_2024_116757
crossref_primary_10_1038_s41598_025_14351_y
crossref_primary_10_1002_smll_202506890
crossref_primary_10_1042_BST20231332
crossref_primary_10_3390_ani13243817
crossref_primary_10_1007_s12017_025_08864_y
crossref_primary_10_1016_j_phyplu_2025_100845
crossref_primary_10_1016_j_chemosphere_2024_142964
crossref_primary_10_1016_j_fgb_2022_103730
crossref_primary_10_1016_j_jep_2024_118414
crossref_primary_10_1371_journal_pone_0286274
crossref_primary_10_1016_j_heliyon_2024_e40654
crossref_primary_10_1080_10408398_2024_2357701
crossref_primary_10_3390_ph17060692
crossref_primary_10_1007_s12088_025_01447_2
crossref_primary_10_1080_13543776_2024_2397732
crossref_primary_10_1002_cbdv_202400709
crossref_primary_10_1016_j_foodres_2025_116124
crossref_primary_10_1016_j_biopha_2025_118091
crossref_primary_10_3389_fceld_2023_1322780
crossref_primary_10_1016_j_chmed_2025_09_005
crossref_primary_10_1016_j_mam_2025_101411
crossref_primary_10_3390_molecules28020796
crossref_primary_10_1016_j_tox_2023_153692
crossref_primary_10_7759_cureus_89916
crossref_primary_10_1039_D5NJ00670H
crossref_primary_10_3389_fphar_2024_1303732
crossref_primary_10_1016_j_arabjc_2023_105192
crossref_primary_10_1016_j_tox_2025_154102
crossref_primary_10_1002_ptr_7870
crossref_primary_10_1111_jcmm_70624
crossref_primary_10_1371_journal_pone_0308095
crossref_primary_10_1002_open_202500252
crossref_primary_10_3389_fphar_2023_1291920
crossref_primary_10_1016_j_jinorgbio_2023_112283
crossref_primary_10_1021_acsptsci_4c00681
crossref_primary_10_1111_bph_16299
crossref_primary_10_3390_md22020057
crossref_primary_10_1186_s12935_025_03828_5
crossref_primary_10_3390_ijms26115066
crossref_primary_10_1080_09546634_2025_2526075
crossref_primary_10_1007_s12032_024_02335_3
crossref_primary_10_1016_j_fct_2024_115218
crossref_primary_10_1371_journal_pone_0332212
crossref_primary_10_1016_j_metabol_2025_156359
crossref_primary_10_1016_j_jtemb_2025_127757
crossref_primary_10_1038_s41598_023_39455_1
crossref_primary_10_3389_fphar_2025_1631977
crossref_primary_10_3390_ijms26062390
crossref_primary_10_1371_journal_pone_0292434
crossref_primary_10_1002_iub_2888
crossref_primary_10_1080_14756366_2024_2311157
crossref_primary_10_1111_apha_14150
crossref_primary_10_1002_jemt_24872
crossref_primary_10_1002_tox_24168
crossref_primary_10_1016_j_ejphar_2022_175426
crossref_primary_10_1111_cbdd_14355
crossref_primary_10_1186_s10020_023_00678_7
crossref_primary_10_3390_ijms252313048
crossref_primary_10_1007_s12013_025_01724_3
crossref_primary_10_1007_s00210_025_04288_4
crossref_primary_10_1515_tjb_2024_0045
crossref_primary_10_2147_JIR_S497775
crossref_primary_10_1111_cns_70481
crossref_primary_10_1016_j_semcdb_2023_06_008
ContentType Journal Article
Copyright 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Copyright_xml – notice: 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
DBID CGR
CUY
CVF
ECM
EIF
NPM
7X8
DOI 10.1042/BCJ20210854
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic
MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Anatomy & Physiology
Chemistry
EISSN 1470-8728
ExternalDocumentID 35147165
Genre Journal Article
GroupedDBID ---
-DZ
-~X
0R~
23N
2WC
4.4
53G
5GY
5RE
6J9
79B
A8Z
AABGO
AAHRG
ABJNI
ABPPZ
ABRJW
ACGFO
ACGFS
ACNCT
ADBBV
AEGXH
AENEX
AIAGR
AIZAD
ALMA_UNASSIGNED_HOLDINGS
BAWUL
CGR
CS3
CUY
CVF
DU5
E3Z
EBD
EBS
ECM
EIF
EMOBN
F5P
H13
HH6
HZ~
K-O
L7B
ML-
MV1
N9A
NPM
NTEUP
O9-
OK1
P2P
RHI
RNS
RPM
RPO
SV3
TR2
TWZ
WH7
XSW
Y6R
YNY
~02
~KM
7X8
ESTFP
ID FETCH-LOGICAL-c355t-e8460de1e643831e92b171deab75619d34bc4de3b155c1682715852f053a23ee2
IEDL.DBID 7X8
ISICitedReferencesCount 205
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001124787200001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1470-8728
IngestDate Wed Oct 01 13:37:23 EDT 2025
Wed Feb 19 02:27:05 EST 2025
IsPeerReviewed true
IsScholarly true
Issue 3
Keywords BCL-2
apoptosis
apoptosome
cell death
caspases
death receptors
Language English
License 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c355t-e8460de1e643831e92b171deab75619d34bc4de3b155c1682715852f053a23ee2
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ORCID 0000-0003-1149-212X
PMID 35147165
PQID 2628299023
PQPubID 23479
ParticipantIDs proquest_miscellaneous_2628299023
pubmed_primary_35147165
PublicationCentury 2000
PublicationDate 2022-02-11
PublicationDateYYYYMMDD 2022-02-11
PublicationDate_xml – month: 02
  year: 2022
  text: 2022-02-11
  day: 11
PublicationDecade 2020
PublicationPlace England
PublicationPlace_xml – name: England
PublicationTitle Biochemical journal
PublicationTitleAlternate Biochem J
PublicationYear 2022
SSID ssj0014040
Score 2.6920075
SecondaryResourceType review_article
Snippet Regulated cell death is a vital and dynamic process in multicellular organisms that maintains tissue homeostasis and eliminates potentially dangerous cells....
SourceID proquest
pubmed
SourceType Aggregation Database
Index Database
StartPage 357
SubjectTerms Animals
Apoptosis - physiology
Apoptosis Regulatory Proteins - physiology
Apoptosomes - physiology
Apoptosomes - ultrastructure
Autophagy
Caspases - physiology
Humans
Invertebrates - cytology
Ligands
Lysosomes - physiology
Macrophages - physiology
Mitochondrial Membranes - physiology
Necrosis
Neoplasm Proteins - physiology
Permeability
Phagocytosis
Proto-Oncogene Proteins c-bcl-2 - physiology
Receptors, Death Domain - physiology
Title The concept of intrinsic versus extrinsic apoptosis
URI https://www.ncbi.nlm.nih.gov/pubmed/35147165
https://www.proquest.com/docview/2628299023
Volume 479
WOSCitedRecordID wos001124787200001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3NS8MwFA_qBL34sfkxv4gg3sKWNGuSk8zhEMGxg8JuJU0T6MG2rp3gf-9L27GTIHjpoVBIXl9efu_zh9Cdih3XLh4SKRUn3FJDtAot4X7UCLNGmCSpySbEbCYXCzVvA25lW1a5tom1oU5y42PkAxb6nJ-CK-ah-CSeNcpnV1sKjW3UCQDKeK0Wi00WgQ-bhkguYC2CybY_D_R08Dh5Yd7dkZ4H4DdsWd8x08P_ru4IHbToEo8bdThGWzbrot44A8_64xvf47resw6kd9HeZM311kMBaAs2TQcjzh1Os2qZZvADsa_aWJUYTHj7Qhd5UeVlWp6g9-nT2-SZtHQKxACoqIgFqDFMLLWhH09KrWIxFTSxOhYAolQS8NjwxAYxQAxDQ8kEBV-COTimmgXWslO0k-WZPUeYOWkkd2Hgp9eETqvAsxabkdOMWzHUfXS7FlMEO_E5CJ3ZfFVGG0H10Vkj66ho5mpEvqkA3LfRxR--vkT7zDcieGoWeoU6Dg6rvUa75qtKy-VNrQfwnM1ffwBzK7wG
linkProvider ProQuest
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+concept+of+intrinsic+versus+extrinsic+apoptosis&rft.jtitle=Biochemical+journal&rft.au=Lossi%2C+Laura&rft.date=2022-02-11&rft.issn=1470-8728&rft.eissn=1470-8728&rft.volume=479&rft.issue=3&rft.spage=357&rft_id=info:doi/10.1042%2FBCJ20210854&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1470-8728&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1470-8728&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1470-8728&client=summon