Apolipoproteins L1 and L3 control mitochondrial membrane dynamics

Lecordier, Laurence; Heo, Paul; Graversen, Jonas H.; Hennig, Dorle; Skytthe, Maria Kløjgaard; Cornet d’Elzius, Alexandre; Pincet, Frédéric; Pérez-Morga, David; Pays, Etienne

doi:10.1016/j.celrep.2023.113528

Cited by 6 publications

(59 citation statements)

References 131 publications

(226 reference statements)

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“…However, the existence of plasma membrane APOL1 pores remains to be demonstrated, and the surface cationic fluxes were not proven to occur through such pores. Since both NCS1 and the PI4KB product phosphatidylinositol-4-phosphate (PI4P) are involved in cation channel activity at the plasma membrane, including K + efflux by Kv4 channels [33][34][35], delocalizing PI4KB and NCS1 activities from the Golgi as occurs upon APOL3-PI4KB complex disruption [11,16] could affect surface cation fluxes independently of APOL1 pores. In addition, and importantly, the intracellular Ca 2+ fluxes could result not from APOL1 pore activity, but from increased NCS1 binding to GPRCs and GPCR kinases [36][37][38][39] as well as NCS1 binding to IP3Rs, including at endoplasmic reticulum-mitochondrion contact sites (MERCSs) [33,39,40].…”

Section: Apol1 and Apol3 Pore-forming Activitymentioning

confidence: 99%

“…APOL1 co-localizes with PI4KB and APOL3 in ATG9A vesicles [16], known to traffic PI4KB from the Golgi to the mitochondrion for autophagy initiation, which occurs together with mitochondrion fission at MERCSs [44,70]. Moreover, APOL1 tightly associates with NM2A, the myosin known to be responsible for ATG9A vesicle trafficking [11,[71][72][73].…”

Section: Apol1 Controls Pi4kb and Apol3 Trafficmentioning

confidence: 99%

“…Moreover, APOL1 tightly associates with NM2A, the myosin known to be responsible for ATG9A vesicle trafficking [11,[71][72][73]. Finally, APOL1 can bind to prohibitin-2 (PHB2) [16], a mitophagy receptor involved in IFN-I-mediated autophagy together with GOLPH3 [74][75][76].…”

Section: Apol1 Controls Pi4kb and Apol3 Trafficmentioning

confidence: 99%

“…Altogether, these observations linked APOLs to cellular killing or toxic activities. However, recent work [ 16 ] has uncovered the crucial involvement of APOL1 and APOL3 in intracellular membrane fission and fusion, suggesting that their basic function is not to induce pathogen lysis, but to control membrane dynamics.…”

Section: Introductionmentioning

confidence: 99%

“…After a long hinge sequence (APOL1 A291-A339; APOL3 A232-T272), a second HC-LZ tandem (HC2-LZ2) characterizes the C-terminal region of both APOLs (APOL1 S342-L392; APOL3 G275-L325). In case of APOL1 but not APOL3, the HC2-LZ2 tandem strongly interacts with HC1-LZ1, imposing a specific protein folding that underlies differential trans -interactions of APOL1 with respect to APOL3 [ 11 , 16 ].

Fig.…”

Section: Introductionmentioning

confidence: 99%

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The Janus-faced functions of Apolipoproteins L in membrane dynamics

Pays

2024

Cell. Mol. Life Sci.

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The functions of human Apolipoproteins L (APOLs) are poorly understood, but involve diverse activities like lysis of bloodstream trypanosomes and intracellular bacteria, modulation of viral infection and induction of apoptosis, autophagy, and chronic kidney disease. Based on recent work, I propose that the basic function of APOLs is the control of membrane dynamics, at least in the Golgi and mitochondrion. Together with neuronal calcium sensor-1 (NCS1) and calneuron-1 (CALN1), APOL3 controls the activity of phosphatidylinositol-4-kinase-IIIB (PI4KB), involved in both Golgi and mitochondrion membrane fission. Whereas secreted APOL1 induces African trypanosome lysis through membrane permeabilization of the parasite mitochondrion, intracellular APOL1 conditions non-muscular myosin-2A (NM2A)-mediated transfer of PI4KB and APOL3 from the Golgi to the mitochondrion under conditions interfering with PI4KB-APOL3 interaction, such as APOL1 C-terminal variant expression or virus-induced inflammatory signalling. APOL3 controls mitophagy through complementary interactions with the membrane fission factor PI4KB and the membrane fusion factor vesicle-associated membrane protein-8 (VAMP8). In mice, the basic APOL1 and APOL3 activities could be exerted by mAPOL9 and mAPOL8, respectively. Perspectives regarding the mechanism and treatment of APOL1-related kidney disease are discussed, as well as speculations on additional APOLs functions, such as APOL6 involvement in adipocyte membrane dynamics through interaction with myosin-10 (MYH10).

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Section: Apol1 and Apol3 Pore-forming Activitymentioning

confidence: 99%

Section: Apol1 Controls Pi4kb and Apol3 Trafficmentioning

confidence: 99%

Section: Apol1 Controls Pi4kb and Apol3 Trafficmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fig.…”

Section: Introductionmentioning

confidence: 99%

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The Janus-faced functions of Apolipoproteins L in membrane dynamics

Pays

2024

Cell. Mol. Life Sci.

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Host restriction factor Rab11a limits porcine epidemic diarrhea virus invasion of cells via fusion peptide-mediated membrane fusion

Song,

Li,

Han

et al. 2024

International Journal of Biological Macromolecules

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APOL1 nephropathy – a population genetics success story

Tabachnikov,

Skorecki,

Kruzel-Davila

2024

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review More than a decade ago, apolipoprotein L1 (APOL1) risk alleles designated G1 and G2, were discovered to be causally associated with markedly increased risk for progressive kidney disease in individuals of recent African ancestry. Gratifying progress has been made during the intervening years, extending to the development and clinical testing of genomically precise small molecule therapy accompanied by emergence of RNA medicine platforms and clinical testing within just over a decade. Recent findings Given the plethora of excellent prior review articles, we will focus on new findings regarding unresolved questions relating mechanism of cell injury with mode of inheritance, regulation and modulation of APOL1 activity, modifiers and triggers for APOL1 kidney risk penetrance, the pleiotropic spectrum of APOL1 related disease beyond the kidney – all within the context of relevance to therapeutic advances. Summary Notwithstanding remaining controversies and uncertainties, promising genomically precise therapies targeted at APOL1 mRNA using antisense oligonucleotides (ASO), inhibitors of APOL1 expression, and small molecules that specifically bind and inhibit APOL1 cation flux are emerging, many already at the clinical trial stage. These therapies hold great promise for mitigating APOL1 kidney injury and possibly other systemic phenotypes as well. A challenge will be to develop guidelines for appropriate use in susceptible individuals who will derive the greatest benefit.

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Apolipoproteins L1 and L3 control mitochondrial membrane dynamics

Cited by 6 publications

References 131 publications

The Janus-faced functions of Apolipoproteins L in membrane dynamics

The Janus-faced functions of Apolipoproteins L in membrane dynamics

Host restriction factor Rab11a limits porcine epidemic diarrhea virus invasion of cells via fusion peptide-mediated membrane fusion

APOL1 nephropathy – a population genetics success story

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