ABSTRACT MFN2 (mitofusin 2) is a mitochondrial outer membrane protein that serves primarily as a mitochondrial fusion protein, which is its best known role but has additional functions in regulating cell biological processes. Multiple func tions include participation in mitochondrial fusion, tethering of mitochondrial endoplasmic reticulum membranes, movement of mitochondria along axons, and control of the quality of mitochondria, which is important for the main tenance of cellular homeostasis. Mitochondrial quality control is a process that includes the exchange of mitochondrial components through mitochondrial fusion and fission, and the removal of dysfunctional mitochondria through autophagy/mitophagy. Macroautophagy/autophagy, as major intracellular machinery for degrading aggregated proteins and damaged organelles, is involved in the occurrence of pathological changes in diabetes, obesity, neu rodegenerative diseases and cancer. Intriguingly, MFN2 has been referred to as a tumor suppressor gene in some forms of cancer. Several studies of the effects of MFN2 mutations have not been conclusive on molecular mechanisms caus ing cellular alterations. We tackled some of these issues in fibroblasts derived from a Charcot-Marie-Tooth disease type 2A (CMT2A) patient with a mutation in the GTPase domain of MFN2. So, in this punctum, we discuss the mechanism whereby mitochondrial MFN2 protein mutation affects autophagy and cell proliferation rate.

Autophagy and proliferation are dysregulated in Charcot-Marie-Tooth disease type 2A cells harboring MFN2 (mitofusin 2) mutation

Paola Zanfardino
Methodology
;
Vittoria Petruzzella
Conceptualization
2022-01-01

Abstract

ABSTRACT MFN2 (mitofusin 2) is a mitochondrial outer membrane protein that serves primarily as a mitochondrial fusion protein, which is its best known role but has additional functions in regulating cell biological processes. Multiple func tions include participation in mitochondrial fusion, tethering of mitochondrial endoplasmic reticulum membranes, movement of mitochondria along axons, and control of the quality of mitochondria, which is important for the main tenance of cellular homeostasis. Mitochondrial quality control is a process that includes the exchange of mitochondrial components through mitochondrial fusion and fission, and the removal of dysfunctional mitochondria through autophagy/mitophagy. Macroautophagy/autophagy, as major intracellular machinery for degrading aggregated proteins and damaged organelles, is involved in the occurrence of pathological changes in diabetes, obesity, neu rodegenerative diseases and cancer. Intriguingly, MFN2 has been referred to as a tumor suppressor gene in some forms of cancer. Several studies of the effects of MFN2 mutations have not been conclusive on molecular mechanisms caus ing cellular alterations. We tackled some of these issues in fibroblasts derived from a Charcot-Marie-Tooth disease type 2A (CMT2A) patient with a mutation in the GTPase domain of MFN2. So, in this punctum, we discuss the mechanism whereby mitochondrial MFN2 protein mutation affects autophagy and cell proliferation rate.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/413352
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact