The Many Faces of Mitochondrial Autophagy: Making Sense of Contrasting Observations in Recent Research

Table 1

Key findings in yeast mitophagy research.

Author	Year	Primary finding	Notes	Assay	Carbon source*	Mitophagy induction*	Reference
Takeshige et al.	1992	Mitochondria within autophagic bodies	First observation of mitochondrial autophagy	Light microscopy, EM	Glucose, glycerol	Shift to N-starvation medium (glucose or glycerol)	[40]
Campbell and Thorsness	1998	Observation of damage-induced mitophagy	Further early evidence of mitophagy	EM	Various (respiratory)	Mitochondrial damage through disruption of YME1	[50]
Kiššová et al.	2004	UTH1	First mitophagy-specific gene identified	pGAL-CLbGFP (fluorescence microscopy)	Lactate & glucose	Shift to N-starvation medium (lactate and glucose) Rapamycin (0.2 μg/mL)	[41]
Priault et al.	2005	Mitochondrial damage triggers mitophagy	Impairing ΔΨ𝑚 results in preferential mitophagy of impaired mitochondria.	EM; Pho8Δ60 (biochemical); Western (protein degradation)	Glucose (aerobic and anaerobic)	Used heat-sensitive Δfmc1 strain to precipitate mitochondrial damage.	[51]
Nowikovsky et al.	2007	MDM38	Found osmotic swelling triggers, and fission and is required for mitophagy	pCS-G/RFP (“Rosella”, microscopy)	Galactose	Doxycyclin (5 μg/mL, induced MDM38 depletion and mitophagy)	[52]
Kiššová et al.	2007	UTH1	Description of selective mitophagy and “micromitophagy.”	EM	Lactate throughout	Shift to N-starvation medium (lactate)	[42]
Tal et al.	2007	AUP1	AUP1 role in post-log phase mitophagy described	Western (aconitase degradation)	Glucose, lactate	Culture to post-log (glucose, lactate, up to 5 d)	[43]
Kanki and Klionsky	2008	ATG11	Further demonstration of selective mitophagy.	OM45-GFP, IDH1-GFP, ALP (biochemical)	Lactate	Shift to N-starvation medium (glucose)	[38]
Deffieu et al.	2009	Glutathione involvement	Indicates role of Redox in mitophagy induction	pGAL-CLbGFP (microscopy); EM	Lactate	Shift to N-starvation medium (glucose)	[53]
Kanki et al.	2009	ATG33 (and 31 others)	Did not report UTH1, MDM38, AUP1, RTG3 or WHI2.; 8 reported genes overlap with Okamoto et al.	OM45-GFP (microscopy and western)	Lactate	Culture to post-log (lactate, 3 d) Shift to N-starvation medium (up to 6 h glucose)	[48]
Kanki et al.	2009	ATG32	Identified at same time as Okamoto et al.	OM45-GFP (microscopy & western)	Lactate	Culture to post-log (lactate, 3 d) Shift to N-starvation media (up to 6 h glucose)	[46]
Okamoto et al.	2009	ATG32 (& 52 others, including some known autophagy genes)	Did not report UTH1, MDM38, AUP1, RTG3, WHI2 or ATG33.; 8 reported genes overlap with Kanki et al.	p416GPD-mtDHFR-GFP (microscopy)	Glycerol	Culture to post-log (glycerol, 5 d)	[45]
Journo et al.	2009	RTG3	Also found RTG3 regulates AUP1.	Fluorescence microscopy & Western analyses IDP1-GFP (microscopy)	Lactate	Culture to post-log (lactate, 3 d)	[44]
Mao et al.	2011	HOG1, SLT2	Shows MAPK signalling is involved in mitophagy in yeast	OM45-GFP(microscopy & western)	Lactate	Shift to N-starvation media (6 h, glucose); Culture to post-log (lactate)	[54]
Mendl et al.	2011	WHI2	Found fission is not essential for mitophagy.	pRS313-mtDsRed.T4 (microscopy)	Glycerol	Rapamycin (1 μM, 24 h, in DMSO)	[55]

*Where “carbon source” and “mitophagy induction” refer to conditions used to detect the primary finding.
GFP = green fluorescent protein, ΔΨ_𝑚 = mitochondrial membrane potential, MOM = mitochondrial outer membrane, EM = electron microscopy, MAPK = mitogen activated protein kinase, N-starvation = nitrogen-starvation.