Neuronal Gtf2i deletion alters mitochondrial and autophagic properties

Ariel Nir Sade, Gilad Levy, Sari Schokoroy Trangle, Galit Elad Sfadia, Ela Bar, Omer Ophir, Inbar Fischer, May Rokach, Andrea Atzmon, Hadar Parnas, Tali Rosenberg, Asaf Marco, Orna Elroy Stein, Boaz Barak

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Gtf2i encodes the general transcription factor II-I (TFII-I), with peak expression during pre-natal and early post-natal brain development stages. Because these stages are critical for proper brain development, we studied at the single-cell level the consequences of Gtf2i’s deletion from excitatory neurons, specifically on mitochondria. Here we show that Gtf2i’s deletion resulted in abnormal morphology, disrupted mRNA related to mitochondrial fission and fusion, and altered autophagy/mitophagy protein expression. These changes align with elevated reactive oxygen species levels, illuminating Gtf2i’s importance in neurons mitochondrial function. Similar mitochondrial issues were demonstrated by Gtf2i heterozygous model, mirroring the human condition in Williams syndrome (WS), and by hemizygous neuronal Gtf2i deletion model, indicating Gtf2i’s dosage-sensitive role in mitochondrial regulation. Clinically relevant, we observed altered transcript levels related to mitochondria, hypoxia, and autophagy in frontal cortex tissue from WS individuals. Our study reveals mitochondrial and autophagy-related deficits shedding light on WS and other Gtf2i-related disorders.

Original languageEnglish
Article number1269
JournalCommunications Biology
Issue number1
StatePublished - 14 Dec 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).


The authors would like to thank the members of the Barak laboratory for their support along the project. Also, we would like to thank Prof. Inna Slutsky, Prof. Eitan Okun, Prof. Ronit Pinkas-Kramarski, and Dr. Avi Ashkenazi for their insightful comments on this study. This research was supported by the ISRAEL SCIENCE FOUNDATION (grant No. 2305/20, awarded to B.B.) Williams France Federation and Autour des Williams (awarded to B.B.).

FundersFunder number
Israel Science Foundation2305/20


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