Mechanisms of mitochondrial reorganization DOI Open Access

Tatsuro Maruyama,

Yutaro Hama, Nobuo N. Noda

и другие.

The Journal of Biochemistry, Год журнала: 2023, Номер 175(2), С. 167 - 178

Опубликована: Ноя. 28, 2023

Abstract The cytoplasm of eukaryotes is dynamically zoned by membrane-bound and membraneless organelles. Cytoplasmic zoning allows various biochemical reactions to take place at the right time place. Mitochondrion a organelle that provides zone for intracellular energy production metabolism lipids iron. A key feature mitochondria their high dynamics: constantly undergo fusion fission, excess or damaged are selectively eliminated mitophagy. Therefore, appropriate model systems understand dynamic cytoplasmic membrane In this review, we summarize molecular mechanisms mitochondrial fission as well mitophagy unveiled through studies using yeast mammalian models.

Язык: Английский

Coordinating BNIP3/NIX-mediated mitophagy in space and time DOI Creative Commons
Natalie M. Niemi, Jonathan R. Friedman

Biochemical Society Transactions, Год журнала: 2024, Номер 52(5), С. 1969 - 1979

Опубликована: Окт. 8, 2024

Mitochondria maintain organellar homeostasis through multiple quality control pathways, including the clearance of defective or unwanted mitochondria by selective autophagy. This removal mitochondria, mitophagy, is controlled in large part outer mitochondrial membrane mitophagy receptors BNIP3 and NIX. While it has long been appreciated that NIX mediate controlling recruitment autophagic machinery to surface, requirement for carefully spatiotemporal regulation receptor-mediated only recently come light. Several new factors regulate BNIP3/NIX-mediated pathway have emerged, various loss-of-function cell animal models revealed dire consequences their dysregulation. In this mini-review, we discuss insights into mechanisms roles highlight questions emerged from identification these regulators.

Язык: Английский

Процитировано

6
WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation DOI Creative Commons
Andrea Gubaš, Eleanor Attridge,

Harold B.J. Jefferies

и другие.

EMBO Reports, Год журнала: 2024, Номер 25(9), С. 3789 - 3811

Опубликована: Авг. 16, 2024

Язык: Английский

Процитировано

3
The LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux DOI

Brian J. North,

Amelia E Ohnstad, Michael J. Ragusa

и другие.

The Journal of Cell Biology, Год журнала: 2025, Номер 224(4)

Опубликована: Янв. 8, 2025

During autophagy, toxic cargo is encapsulated by autophagosomes and trafficked to lysosomes for degradation. NBR1, an autophagy receptor targeting ubiquitinated aggregates, serves as a model studying the multivalent, heterotypic interactions of cargo-bound receptors. Here, we find that three critical NBR1 partners—ATG8-family proteins, FIP200, TAX1BP1—each bind distinct, overlapping determinants within short linear interaction motif (SLiM). To explore whether SLiMs extend beyond analyzed >100 LC3-interacting regions (LIRs), revealing FIP200 and/or TAX1BP1 binding LIRs common phenomenon suggesting protein hotspots. Phosphomimetic peptides demonstrate phosphorylation generally enhances ATG8-family but not TAX1BP1, indicating differential regulation. In vivo, LIR-mediated with promote optimal flux leveraging additional functionalities from TAX1BP1. These findings reveal one-to-many modality in LIR illustrating cooperative mechanisms receptors regulatory potential multifunctional SLiMs.

Язык: Английский

Процитировано

0
Transcriptional Dynamics Uncover the Role of BNIP3 in Mitophagy during Muscle Remodeling in Drosophila DOI Open Access

Hiroki Taoka,

Tadayoshi Murakawa,

Kohei Kawaguchi

и другие.

Опубликована: Март 12, 2025

Differentiated muscle cells contain myofibrils and well-organized organelles, enabling powerful contractions. Muscle cell reorganization occurs in response to various physiological stimuli; however, the mechanisms behind this remodeling remain enigmatic due lack of a genetically trackable system. Previously, we reported that subset larval is remodeled into adult abdominal through an autophagy-dependent mechanism Drosophila . To unveil underlying remodeling, performed comparative time-course RNA-seq analysis isolated with or without autophagy. It revealed both transcriptional dynamics independent autophagy highlighted significance BNIP3-mediated mitophagy remodeling. Mechanistically, found BNIP3 recruits autophagic machinery mitochondria its LC3-interacting (LIR) motif minimal essential region (MER), which interact Atg8a Atg18a, respectively. Loss leads substantial accumulation mitochondria, ultimately impairing In summary, study demonstrates BNIP3-dependent critical for orchestrating dynamic process

Язык: Английский

Процитировано

0
Transcriptional Dynamics Uncover the Role of BNIP3 in Mitophagy during Muscle Remodeling in Drosophila DOI Open Access

Hiroki Taoka,

Tadayoshi Murakawa,

Kohei Kawaguchi

и другие.

Опубликована: Март 12, 2025

Differentiated muscle cells contain myofibrils and well-organized organelles, enabling powerful contractions. Muscle cell reorganization occurs in response to various physiological stimuli; however, the mechanisms behind this remodeling remain enigmatic due lack of a genetically trackable system. Previously, we reported that subset larval is remodeled into adult abdominal through an autophagy-dependent mechanism Drosophila . To unveil underlying remodeling, performed comparative time-course RNA-seq analysis isolated with or without autophagy. It revealed both transcriptional dynamics independent autophagy highlighted significance BNIP3-mediated mitophagy remodeling. Mechanistically, found BNIP3 recruits autophagic machinery mitochondria its LC3-interacting (LIR) motif minimal essential region (MER), which interact Atg8a Atg18a, respectively. Loss leads substantial accumulation mitochondria, ultimately impairing In summary, study demonstrates BNIP3-dependent critical for orchestrating dynamic process

Язык: Английский

Процитировано

0
Advances in mitophagy initiation mechanisms DOI Creative Commons
Catharina J. Küng, Michael Lazarou, Thanh Ngoc Nguyen

и другие.

Current Opinion in Cell Biology, Год журнала: 2025, Номер 94, С. 102493 - 102493

Опубликована: Март 21, 2025

Язык: Английский

Процитировано

0
The Role of WIPI2, ATG16L1 and ATG12-ATG5 in selective and nonselective autophagy DOI Creative Commons
Daniele Campisi,

Nessa Hawkins,

Kennedy Bonjour

и другие.

Journal of Molecular Biology, Год журнала: 2025, Номер unknown, С. 169138 - 169138

Опубликована: Апрель 1, 2025

Autophagy is a conserved cellular recycling pathway that delivers damaged or superfluous cytoplasmic material to lysosomes for degradation. In response cytotoxic stress starvation, autophagy can also sequester bulk cytoplasm and deliver it regenerate building blocks. macroautophagy, membrane cisterna termed phagophore encloses autophagic cargo generated. The formation of the depends on machinery related proteins. phosphatidylinositol(3)-phosphate binding protein WIPI2 facilitates transition from initiation expansion by recruiting ATG12-ATG5-ATG16L1 complex phagophores. This functions as an E3-ligase conjugate ubiquitin-like ATG8 proteins membranes, which promotes tethering expansion, maturation fusion autophagosomes with lysosomes. ATG16L1 has important independently ATG12-ATG5 in beyond. this review, we will summarize selective nonselective autophagy.

Язык: Английский

Процитировано

0
The mitophagy receptors BNIP3 and NIX mediate tight attachment and expansion of the isolation membrane to mitochondria DOI Creative Commons
Shun‐ichi Yamashita, Ritsuko Arai,

Hiroshi Hada

и другие.

The Journal of Cell Biology, Год журнала: 2025, Номер 224(7)

Опубликована: Май 13, 2025

BNIP3 and NIX are the main receptors for mitophagy, but their mechanisms of action remain elusive. Here, we used correlative light EM (CLEM) electron tomography to reveal tight attachment isolation membranes (IMs) mitochondrial protrusions, often connected with ER via thin tubular and/or linear structures. In BNIP3/NIX-double knockout (DKO) HeLa cells, ULK1 complex nascent IM formed on mitochondria, did not expand. Artificial tethering LC3B mitochondria induced mitophagy that was equally efficient in DKO cells WT cells. accumulated at segregated protrusions binding LC3 through LIR motifs require dimer formation. Finally, average distance between surface receptor-mediated significantly smaller than ubiquitin-mediated mitophagy. Collectively, these results indicate required expansion along during

Язык: Английский

Процитировано

0
Presynapses are mitophagy pit stops that prevent axon degeneration DOI Creative Commons
Wai Kit Lam, Runa Lindblom, Bridget Milky

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

Abstract Defects in neuronal mitophagy have been linked to neurodegenerative diseases including Parkinson’s disease. However, despite the importance of homeostasis, mechanistic basis for neurodegeneration when is defective unclear. Here, using human neurons, we discover that presynapses are pit stops damaged axonal mitochondria. We show while mitochondrial damage and PINK1/Parkin activation events distributed throughout axons, initiation autophagosome formation restricted presynapses, which contain machineries required mitophagy. Being primary sites mitophagy, were vulnerable was defective. observed local cytochrome c release within from an accumulation This resulted downstream degradative caspase activation, defining a mechanism neurodegeneration. Pharmacological rescue axon degeneration achieved through synthetic upregulation receptor mediated with clinically approved compound Roxadustat, revealing potential therapeutic avenue

Язык: Английский

Процитировано

2
Human WIPI β‐propeller function in autophagy and neurodegeneration DOI Creative Commons
Tassula Proikas‐Cezanne,

Maximilian L. Haas,

Carmen J. Pastor‐Maldonado

и другие.

FEBS Letters, Год журнала: 2023, Номер 598(1), С. 127 - 139

Опубликована: Дек. 7, 2023

The four human WIPI β-propellers, WIPI1 through WIPI4, belong to the ancient PROPPIN family and fulfill scaffold functions in control of autophagy. In this context, β-propellers function as PI3P effectors during autophagosome formation loss negatively impacts autophagy contributes neurodegeneration. Of particular interest are mutations WDR45, gene that encodes WIPI4. Sporadic WDR45 cause a rare neurodegenerative disease called BPAN, hallmarked by high brain iron accumulation. Here, we discuss current understanding address unanswered questions with focus on role WIPI4 BPAN.

Язык: Английский

Процитировано

4