TABLE 1.

Other mitochondrial and non-mitochondrial proteins impacting β-cell mitochondrial function. Protein name and localization verified on Uniprot, general physiologic roles and β-cell-specific roles are described.

Protein	Location	General physiologic role	β-cell-specific roles
MPV17 (MPV17L2)	Mitochondrial inner membrane	ROS balance; maintains, ETC, MMP, and folate metabolism Madungwe et al. (2020), Jacinto et al. (2021), Spinazzola et al. (2006), Alonzo et al. (2018)	• KO mice reduces apoptosis in diabetic stress Tang et al. (2023)
MRPL59 (CRIF1, PRG6, PLINP1)	Mitochondrial inner membrane	Insertion of nascent proteins into inner mitochondrial membrane for, ETC complex; positive and negative regulation of proliferation Kim et al. (2012), Horikoshi et al. (1999), Nakayama et al. (2007)	• Decreased expression in human T2D islets; haploinsufficient mice have decreased insulin secretion and increased hyperglycemia Hong et al. (2022)
TFB1M (mtTFB1)	Mitochondria	Mitochondrial transcriptional co-activator of TFAM; tissue-specific methylation of mitochondrial rRNA (16S and 12S) McCulloch et al. (2002), Seidel-Rogol et al. (2003), Metodiev et al. (2009), Lee et al. (2015b)	• SNP in gene increases risk of T2D in humans; expression correlates with GSIS; Haploinsufficient mice have decreased GSIS Koeck et al. (2011)
DIMT1	Nucleoli, cytoplasm	Methylation of 18s rRNA, ribosome assembly Zorbas et al., 2015	• Knockdown in human cell lines and rat islets reduces OXPHOS, ATP synthesis, and GSIS Verma et al. (2022)
PAK1 (Alpha-PAK)	Cytoplasm, Plasma membrane, Nucleus	Integrin and receptor-type kinases signaling; cell structure, adhesion, migration, proliferation, apoptosis, mitosis, and vesicle transport Harms et al. (2018), Manabe et al. (2002), Rider et al. (2007), Zhou et al. (2003), Zhou and Kramer (2005)	• Reduced in islets of T2D patients Wang et al. (2011)
			• Overexpression in human islets reduces ER stress markers; KO in mice reduces glucose clearance, GSIS, and complex I; increases apoptosis and ROS Ahn et al. (2021)
			• MIN6 cell proliferation Chen et al. (2013)
CD63 (LAMP-3)	Cell Surface	Surface receptor for TIMP1, integrin signaling and activation of ITGB1 Lee et al. (2014b), Tugues et al. (2013)	• Decreased expression in HFD mice and T2D; increased GSIS, OCR in high expressing mouse and human β-cells Rubio-Navarro et al. (2023)
			• Insulin degranulation; KO mice had increased GSIS Pasquier et al. (2019)
AMPK (PRKAA1/2)	Cytoplasm, Nucleus	Energy sensor, protein kinase, metabolism, autophagy, cell growth, mitochondrial homeostasis Herzig and Shaw (2018), Towler and Hardie (2007), Hardie (2007)	• β-cell KO have reduced insulin content, mild hyperglycemia and increased proliferation Sun et al. (2010)
			• AMPK activation protects against ER and mitochondrial defects, and β-cell apoptosis in diabetic stress Wikstrom et al. (2013)
LKB1 (STK11, PJS)	Cytoplasm, Nucleus	Energy sensor, protein kinase, activates AMPK family members, cell metabolism, cell polarity, apoptosis, and DNA damage response Karuman et al. (2001), Gurumurthy et al. (2010)	• β-cell KO in mice increases insulin secretion, β-cell size, and mass, causes mitochondrial defects Swisa et al. (2015), Granot et al. (2009), Fu et al. (2015), Fu et al. (2009)
MOTS-c (MT-RNR1)	Mitochondria, Plasma membrane, Nucleus	Metabolic homeostasis, protects against obesity and insulin resistance, mutation associated with T2D Lee et al. (2015a), Zempo et al. (2021)	• Anti-inflammatory properties in NOD mice, reduces T-cell-mediated β-cell death Kong et al. (2021)
			• Reduced in T2D associated with poor glycemic control Du et al. (2018)
BAX (BCL2L4)	Cytoplasm, Nucleus, Mitochondrial outer membrane	Pro-apoptotic Pena-Blanco and Garcia-Saez (2018)	• Activates mitochondrial apoptosis White et al. (2020), McKenzie et al. (2010)
			• Amplifies UPR with BAK to exacerbate gluco/lipotoxicity White et al. (2020)
BAK (BAK1, BCL2L7, CDN1)	Mitochondrial outer membrane	Pro-apoptotic Chittenden et al. (1995)	• Activates mitochondrial apoptosis White et al. (2020)
			• Amplifies UPR with BAX to exacerbate gluco/lipotoxicity White et al. (2020)